Published on January 21, 2020
slide 1: Tel: 1-631-504-6093 Fax: 1-631-614-7828 E-mail: infobocsci.com 45-16 Ramsey Road Shirley NY 11967 USA VEGFR Inhibitors inhibitors agonists and modulators Vascular endothelial growth factor VEGF is an important signaling protein involved in both vasculogenesis the formation of the circulatory system and angiogenesis the growth of blood vessels from pre-existing vasculature. slide 2: www.bocsci.com 2 / 33 Sorafenib - CAS 284461-73-0 Catalog Number: B0084-065081 Price: 149/1 g Molecular Weight: 464.82 Molecular Formula: C21H16ClF3N4O3 Description: Sorafenib is a multikinase inhibitor of Raf-1 B-Raf and VEGFR-2 with IC50 of 6 nM 22 nM and 90 nM respectively. BIBF 1202 - CAS 894783-71-2 Catalog Number: B0084-474893 Price: 458/50 mg Molecular Weight: 525.60 Molecular Formula: C30H31N5O4 Description: BIBF 1202 is the major in-vivo metabolite of BIBF 1120 which is an oral triple angiokinase inhibitor targeting VEGFR PDGFR FGFR. It is a related compound of Intedanib which is an indolinone derivative that inhibits angiokinase and an antitumor agent. It is a novel treatment modality in oncology through blockade of the vascular endothelial growth factor VEGF signaling pathway thus inhibition of tumor angiogenesis. SU 4312 - CAS 5812-07-7 Catalog Number: B0084-357203 Price: 198/50 mg Molecular Weight: 264.33 Molecular Formula: C17H16N2O Description: SU 4312 is a potent and selective inhibitor of VEGFR and PDGFR tyrosine kinases IC50 0.8 and 19.4 μM respectively wirth selectivity over EGFR and c-Src tyrosine kinases. Semaxanib - CAS 204005-46-9 Catalog Number: B0084-352931 Price: 198/100 mg Molecular Weight: 238.28 Molecular Formula: C15H14N2O Description: Semaxanib is a quinolone derivative with potential antineoplastic activity. Semaxanib reversibly inhibits ATP binding to the tyrosine kinase domain of vascular endothelial growth factor receptor 2 VEGFR2 which may inhibit VEGF-stimulated endothelial cell migration and proliferation and reduce the tumor microvasculature. This agent also inhibits the phosphorylation of the stem cell factor receptor tyrosine kinase c-kit often expressed in acute myelogenous leukemia cells. slide 3: www.bocsci.com 3 / 33 OSI-930 - CAS 728033-96-3 Catalog Number: B0084-286626 Price: 198/10 mg Molecular Weight: 443.444 Molecular Formula: C22H16F3N3O2S Description: OSI-930 is a selective thiophene-derived tyrosine kinase inhibitor with potential antineoplastic activity. Tyrosine kinase inhibitor OSI-930 inhibits stem cell factor receptor c-Kit and the vascular endothelial growth factor receptor 2 VEGFR2 which may result in the inhibition of both tumor cell proliferation and tumor angiogenesis. Both c-Kit and VEGFR2 are overexpressed in a variety of cancers. WHI-P180 - CAS 211555-08-7 Catalog Number: B0084-312568 Price: 198/10 mg Molecular Weight: 297.31 Molecular Formula: C16H15N3O3 Description: WHI-P180 moderately inhibited ABCG2 function exhibiting weak phototoxicity. The elimination half-life of WHI-P180 in CD-1 mice BALB/ c mice following i.v. i.p. or p.o. administration was less than 10 min. Systemic clearance of WHI-P180 was 6742 mL/h/kg in CD-I mice and 8188 mL/h/kg in BALB/c mice. Notably WHI-P180 when administered in two consecutive nontoxic i.p. bolus doses of 25 mg/kg inhibited IgE/antigen-induced vascular hyperpermeability in a well-characterized murine model of passive cutaneous anaphylaxis. BIBF 1120 esylate - CAS 656247-18-6 Catalog Number: B0084-434827 Price: 278/500 mg Molecular Weight: 649.76 Molecular Formula: C33H39N5O7S Description: Nintedanib esylate is a potent triple angiokinase inhibitor for VEGFR1/2/3 FGFR1/2/3 and PDGFR α/ β. Motesanib - CAS 453562-69-1 Catalog Number: B0084-069090 Price: 288/100 mg Molecular Weight: 373.45 Molecular Formula: C22H23N5O Description: Motesanib is a multikinase inhibitor that selectively targets VEGF receptors platelet- derived growth factor receptors PDGFRs and Kit receptors. It also potently inhibits angiogenesis and induces regression in tumor xenografts. slide 4: www.bocsci.com 4 / 33 hVEGF-IN-1 - CAS 1637443-98-1 Catalog Number: B0084-267747 Price: 228/2 mg Molecular Weight: 581.75 Molecular Formula: C34H43N7O2 Description: hVEGF-IN-1 inhibits human VEGF-A translation and has antitumor activity. Tumor bearing mice treated with hVEGF-IN-1 have an average tumor volume of less than 300 mm. The tumor weight in the presence of hVEGF-IN-1 reduces around 60.1 to a final weight of 0.18 g. No significant change in body weight is observed during the treatment. Ponatinib - CAS 943319-70-8 Catalog Number: B0084-272000 Price: 198/300 mg Molecular Weight: 532.56 Molecular Formula: C29H27F3N6O Description: Ponatinib is a novel potent multi-target inhibitor of Abl PDGFR α VEGFR2 FGFR1 and Src with IC50 of 0.37 nM 1.1 nM 1.5 nM 2.2 nM and 5.4 nM respectively. SU 4942 - CAS 76086-99-2 Catalog Number: B0084-284846 Price: 198/50 mg Molecular Weight: 300.155 Molecular Formula: C15H10BrNO Description: SU 4942 is a modulator of tyrosine kinase signal transduction targeting VEGF and ECGF. Motesanib Diphosphate - CAS 857876-30-3 Catalog Number: B0084-153042 Price: 158/50 mg Molecular Weight: 569.44 Molecular Formula: C22H29N5O9P2 Description: Motesanib Diphosphate is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM respectively similar activity against Kit 10-fold more selective for VEGFR than PDGFR and Ret. AG 1406 - CAS 71308-34-4 Catalog Number: B0084-284859 Price: 198/25 mg Molecular Weight: 254.333 Molecular Formula: C16H18N2O Description: AG 1406 is an inhibitor of tyrosine phosphorylation. slide 5: www.bocsci.com 5 / 33 Sunitinib Malate - CAS 341031-54-7 Catalog Number: B0084-187069 Price: 398/1 g Molecular Weight: 532.56 Molecular Formula: C22H27FN4O2.C4H6O5 Description: Sunitinib marketed as Sutent by Pfizer and previously known as SU11248 is an oral small-molecule multi-targeted receptor tyrosine kinase RTK inhibitor that was approved by the FDA for the treatment of renal cell carcinoma RCC and imatinib-resistant gastrointestinal stromal tumor GIST on January 26 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications. Nintedanib - CAS 656247-17-5 Catalog Number: B0084-262244 Price: 279/500 mg Molecular Weight: 539.62 Molecular Formula: C31H33N5O4 Description: Nintedanib BIBF 1120 is a potent triple angiokinase inhibitor for VEGFR1/2/3 FGFR1/2/3 and PDGFR α/ β with IC50 of 34 nM/13 nM/13 nM 69 nM/37 nM/108 nM and 59 nM/65 nM. It exhibits potential antiangiogenic and antineoplastic activities. SU 5205 - CAS 3476-86-6 Catalog Number: B0084-284844 Price: 198/50 mg Molecular Weight: 239.249 Molecular Formula: C15H10FNO Description: SU5205 is a VEGFR2 inhibitor. Toceranib phosphate - CAS 874819-74-6 Catalog Number: B0084-463666 Price: 149/1 g Molecular Weight: 494.45 Molecular Formula: C22H28FN4O6P Description: Toceranib phosphate is a kinase inhibitor with both antitumor and antiangiogenic activity through inhibition of KIT vascular endothelial growth factor receptor 2 and PDGFR β. It is a receptor tyrosine kinase inhibitor and is used in the treatment of canine mast cell tumor also called mastocytoma. It may also have an anti-angiogenic effect. slide 6: www.bocsci.com 6 / 33 JK-P3 - CAS 942655-44-9 Catalog Number: B0084-284855 Price: 198/25 mg Molecular Weight: 323.352 Molecular Formula: C18H17N3O3 Description: JK-P3 is a VEGFR2 inhibitor with IC50 values of 7.8 μM. JK-P3 inhibits FGFR 1/3 kinase activity in vitro but exhibits no effect on FGFR signaling in cell-based assays. It suppresses wound healing and tube formation in HUVEC without effecting endothelial cell proliferation. KDR-in-4 - CAS 408502-06-7 Catalog Number: B0084-007571 Molecular Weight: 391.46 Molecular Formula: C23H25N3O3 Description: A potent kinase insert domain-containing receptor KDR/VEGFR2 inhibitor IC50 7 nM Sulfatinib - CAS 1308672-74-3 Catalog Number: B0084-007822 Molecular Weight: 480.58 Molecular Formula: C24H28N6O3S Description: Sulfatinib an oral drug candidate is a small molecule inhibitor of vascular endothelial growth factor receptors VEGFR 1 2 and 3 and the fibroblast growth factor receptor type 1 FGFR1. Sulfatinib exhibited an acceptable safety profile and encouraging antitumor activity in patients with advanced solid tumors particularly neuroendocrine tumors. Vatalanib succinate - CAS 212142-18-2 Catalog Number: B0084-014541 Molecular Weight: 464.9 Molecular Formula: C20H15ClN4.C4H6O4 Description: Vatalanib succinate is a potent and orally bioactive VEGFR inhibitor IC50 37 and 77 nM for VEGFR-2 and -1 respectively exhibiting potential antineoplastic activity. Vatalanib binds to the protein kinase domain of VEGFR and inhibits proliferation migration and survival of HUVECs in vitro. Vatalanib also inhibits PDGFR- β c-Kit and c-Fms. slide 7: www.bocsci.com 7 / 33 E 3810 dihydrochloride Catalog Number: B0084-054865 Molecular Weight: 516.42 Molecular Formula: C26H25N3O4.2HCl Description: E 3810 dihydrochloride is a dual VEGFR/FGFR tyrosine kinase inhibitor. It suppresses the tumor angiogenesis and tumor cell proliferation via inhibiting VEGFR1 -2 and -3 and FGFR-1 and -2 kinases in the nanomolar range. Cediranib dihydrochloride - CAS 288383-20-0 Catalog Number: B0084-065171 Molecular Weight: 450.5 Molecular Formula: C25H27FN4O3 Description: Cediranib AZD-2171 tentative trade name Recentin is a potent inhibitor of vascular endothelial growth factor VEGF receptor tyrosine kinases.The drug is being developed by AstraZeneca as a possible anti-cancer chemotherapeutic agent for oral administration. Pazopanib - CAS 444731-52-6 Catalog Number: B0084-068950 Molecular Weight: 437.52 Molecular Formula: C21H23N7O2S Description: Pazopanib is a novel multi-target inhibitor of VEGFR1 VEGFR2 VEGFR3 PDGFR FGFR c-Kit and c-Fms with IC50 of 10 nM 30 nM 47 nM 84 nM 74 nM 140 nM and 146 nM respectively. Sorafenib Tosylate - CAS 475207-59-1 Catalog Number: B0084-069361 Molecular Weight: 637.03 Molecular Formula: C21H16ClF3N4O3.C7H8O3S Description: Sorafenib Tosylate Bay 43-9006 is a multikinase inhibitor of Raf-1 B-Raf and VEGFR-2 with IC50 of 6 nM 22 nM and 90 nM respectively. Chloropyramine hydrochloride - CAS 6170-42-9 Catalog Number: B0084-073277 Molecular Weight: 326.26 Molecular Formula: C16H20ClN3.HCl Description: Chloropyramine hydrochloride slide 8: www.bocsci.com 8 / 33 Vatalanib dihydrochloride - CAS 212141-51-0 Catalog Number: B0084-087399 Molecular Weight: 419.73 Molecular Formula: C20H15ClN4.2HCl Description: Vatalanib PTK787 ZK-222584 CGP-79787 is an inhibitor of VEGFR2/KDR with IC50 of 37 nM less potent against VEGFR1/Flt-1 18-fold against VEGFR3/Flt-4. SU5402 - CAS 215543-92-3 Catalog Number: B0084-087527 Molecular Weight: 296.32054 Molecular Formula: C17H16N2O3 Description: SU5402 is a potent and selective vascular endothelial growth factor receptor VEGFR and fibroblast growth factor receptor FGFR inhibitor. CP-547632 - CAS 252003-65-9 Catalog Number: B0084-088558 Molecular Weight: 532.405 Molecular Formula: C20H24BrF2N5O3S Description: CP-547632 is as a potent inhibitor of the VEGFR-2 and basic fibroblast growth factor FGF kinases IC50 11 and 9 nM respectively. It is selective relative to epidermal growth factor receptor platelet-derived growth factor and other related TKs. It also inhibits VEGF-stimulated autophosphorylation of VEGFR-2 in a whole cell assay with an IC50 value of 6 nM. After oral administration of CP-547632 to mice bearing NIH3T3/H-ras tumors VEGFR-2 phosphorylation in tumors was inhibited in a dose-dependent fashion EC50 590 ng/ml. CP-547632 is a well- tolerated orally-bioavailable inhibitor presently under clinical investigation for the treatment of human malignancies. Dovitinib - CAS 405169-16-6 Catalog Number: B0084-091881 Molecular Weight: 392.429 Molecular Formula: C21H21FN6O Description: Dovitinib TKI258 potently inhibited FLT3 c-KIT FGFR VEGFR1/2/3 PDGFRß and CSF-1R with IC50 values of 1 2 5 10 8 27 36 nM respectively. Dovitinib selectively blocked the growth of wild-type WT or activated mutant FGFR3-transformed B9 cells and human myeloma cell lines. Dovitinib was an effective treatment in a xenograft mouse model of FGFR3 multiple myeloma. slide 9: www.bocsci.com 9 / 33 Lenvatinib - CAS 417716-92-8 Catalog Number: B0084-092131 Molecular Weight: 426.85 Molecular Formula: C21H19ClN4O4 Description: Lenvatinib E7080 is a multi-target inhibitor mostly for VEGFR2KDR/VEGFR3Flt- 4 with IC50 of 4 nM/5.2 nM less potent against VEGFR1/Flt-1 10-fold more selective for VEGFR2/3 against FGFR1 PDGFR α/ β. Telatinib - CAS 332012-40-5 Catalog Number: B0084-108953 Molecular Weight: 409.83 Molecular Formula: C20H16ClN5O3 Description: Telatinib is a potent inhibitor of VEGFR2/3 c-Kit and PDGFR α with IC50 of 6 nM/4 nM 1 nM and 15 nM respectively. H-Glu-Trp-OH - CAS 38101-59-6 Catalog Number: B0084-114382 Molecular Weight: 333.34 Molecular Formula: C16H19N3O5 Description: H-Glu-Trp-OH inhibits VEGF which may inhibit angiogenesis. E-FeCP-oxindole - CAS 884338-18-5 Catalog Number: B0084-119097 Molecular Weight: 329.17 Molecular Formula: C19H15FeNO Description: E-FeCP-oxindole is a human vascular endothelial cell growth factor receptor 2 VEGFR-2 inhibitor IC50 214 nM. E-FeCP-oxindole exhibits anticancer activity IC50 1 μM against B16 murine melanoma lines. Z-FeCP-oxindole - CAS 1137967-28-2 Catalog Number: B0084-119101 Molecular Weight: 329.17 Molecular Formula: C19H15FeNO Description: Z-FeCP-oxindole is a human vascular endothelial cell growth factor receptor 2 VEGFR-2 inhibitor IC50 220 nM. Z-FeCP-oxindole exhibits anticancer activity IC50 1 μM against B16 murine melanoma lines. slide 10: www.bocsci.com 10 / 33 BMS 605541 - CAS 639858-32-5 Catalog Number: B0084-119119 Molecular Weight: 401.43 Molecular Formula: C19H17F2N5OS Description: BMS 605541 is a potent and ATP-competitive VEGFR-2 inhibitor IC50 23 nM displaying 10-fold selectivity for VEGFR-2 over VEGFR-1. It exhibits antitumor activity in human lung and colon tumor xenograft models. Pazopanib HCl - CAS 635702-64-6 Catalog Number: B0084-146188 Molecular Weight: 473.98 Molecular Formula: C21H23N7O2· HCl Description: Pazopanib is a novel multi-target inhibitor of VEGFR1 VEGFR2 VEGFR3 PDGFR FGFR c-Kit and c-Fms with IC50 of 10 nM 30 nM 47 nM 84 nM 74 nM 140 nM and 146 nM respectively. Brivanib - CAS 649735-46-6 Catalog Number: B0084-146707 Molecular Weight: 370.37756 Molecular Formula: C19H19FN4O3 Description: Brivanib is the hydrolyzed form of Brivanib alaninate which is a vascular endothelial growth factor receptor 2 VEGFR2 inhibitor with potential antineoplastic activity. Brivanib strongly binds to and inhibits VEGFR2 a tyrosine kinase receptor expressed almost exclusively on vascular endothelial cells inhibition of VEGFR2 may result in inhibition of tumor angiogenesis inhibition of tumor cell growth and tumor regression. Check for active clinical trials or closed clinical trials using this agent. Brivanib alaninate - CAS 649735-63-7 Catalog Number: B0084-146708 Molecular Weight: 441.45 Molecular Formula: C22H24FN5O4 Description: Brivanib alaninate is the alaninate ester of a vascular endothelial growth factor receptor 2 VEGFR2 inhibitor with potential antineoplastic activity. Brivanib strongly binds to and inhibits VEGFR2 a tyrosine kinase receptor expressed almost exclusively on vascular endothelial cells inhibition of VEGFR2 may result in inhibition of tumor angiogenesis inhibition of tumor cell growth and tumor regression. Check for active clinical trials or closed clinical trials using this agent. slide 11: www.bocsci.com 11 / 33 Regorafenib - CAS 755037-03-7 Catalog Number: B0084-151007 Molecular Weight: 482.83 Molecular Formula: C21H15ClF4N4O3 Description: Regorafenib also known as BAY 73-4506 is an orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors VEGFRs 2 and 3 and Ret Kit PDGFR and Raf kinases which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis the receptor tyrosine kinases RET KIT and PDGFR and the serine/threonine-specific Raf kinase are involved in tumor cell signaling. Regorafenib is demonstrated to increase the overall survival of patients with metastatic colorectal cancer and has been approved by the US FDA on September 27 2012. Linifanib - CAS 796967-16-3 Catalog Number: B0084-151820 Molecular Weight: 375.407 Molecular Formula: C21H18FN5O Description: Description of Linifanib: Linifanib is an orally bioavailable small-molecule receptor tyrosine kinase RTK inhibitor with potential antineoplastic activity. Linifanib inhibits members of the vascular endothelial growth factor VEGF and platelet-derived growth factor PDGF receptor families it exhibits much less activity against unrelated RTKs soluble tyrosine kinases or serine/threonine kinases. This agent does not have a general antiproliferative effect due to its high dose requirement. However linifanib may exhibit potent antiproliferative and apoptotic effects on tumor cells whose proliferation is dependent on mutant kinases such as fms-related tyrosine kinase receptor-3 FLT3. foretinib - CAS 849217-64-7 Catalog Number: B0084-152657 Molecular Weight: 632.665 Molecular Formula: C34H34F2N4O6 Description: Potent inhibitor of MET VEGFR2 Ron and AXL IC50 values are 0.4 0.9 3 and 11 nM respectively. Also potently inhibits Tie-2 Flt-1 Flt-3 Flt-4 KIT PDGFRalpha and PDGFRbeta. Inhibits migration and invasion of B16F10 melanoma cells in vitro. Suppresses B16F10 tumor growth and metastasis in mice. slide 12: www.bocsci.com 12 / 33 MGCD-265 - CAS 875337-44-3 Catalog Number: B0084-153700 Molecular Weight: 517.60 Molecular Formula: C26H20FN5O2S2 Description: MGCD-265 is a potent multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM 3 nM/3 nM/4 nM respectively and also inhibits Ron and Tie2. ENMD-2076 - CAS 934353-76-1 Catalog Number: B0084-156198 Molecular Weight: 375.47 Molecular Formula: C21H25N7 Description: ENMD-2076 is an orally-active Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis cell division and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers. ENMD-2076 has shown promising activity in Phase 1 clinical trials in solid tumor cancers leukemia and multiple myeloma. ENMD- 2076 is currently in a Phase 2 trial for ovarian cancer and preclinical and clinical activities are ongoing in assessing the compounds applicability for other forms of cancer. ZM 306416 hydrochloride - CAS 196603-47-1 Catalog Number: B0084-170446 Molecular Weight: 370.21 Molecular Formula: C16H13N3O2FCl.HCl Description: ZM 306416 hydrochloride is an inhibitor of vascular endothelial growth factor VEGF receptor tyrosine kinase with 3-fold selectivity over FGFR-1. ZM 306416 hydrochloride inhibits activity of KDR and FLT VEGF receptors IC50 100 nM and 2 μM respectively. Ki8751 - CAS 228559-41-9 Catalog Number: B0084-175350 Molecular Weight: 469.41 Molecular Formula: C24H18F3N3O4 Description: Ki8751 is a potent selective inhibitor of VEGFR-2 tyrosine kinase IC50 0.9 nM. Displays some inhibitory activity towards c-Kit PDGFR α and FGFR-2 IC50 values range from 40 to 170 nM. slide 13: www.bocsci.com 13 / 33 NVP-ACC789 - CAS 300842-64-2 Catalog Number: B0084-178779 Molecular Weight: 405.3 Molecular Formula: C21H17BrN4 Description: NVP-ACC789 is a potent selective and orally active inhibitor of the VEGF receptor tyrosine kinases antagonizing tumor-driven angiogenesis Ramucirumab - CAS 947687-13-0 Catalog Number: B0084-185679 Molecular Weight: 143609.68 Molecular Formula: C6374H9864N1692O1996S46 Description: Ramucirumab is a human IgG1 monoclonal antibody developed by ImClone Systems Inc to treat solid tumors. It has been approved by FDA for the treatment of advanced gastric or gastro-esophageal junction adenocarcinoma and metastatic non-small-cell lung carcinoma NSCLC. Ramucirumab acts as a VEGFR2 antagonist via binding to VEGFR2. Sunitinib - CAS 557795-19-4 Catalog Number: B0084-186154 Molecular Weight: 398.47 Molecular Formula: C22H27FN4O2 Description: Sunitinib is a multi-targeted RTK inhibitor targeting VEGFR2 Flk-1 and PDGFR β with IC50 of 80 nM and 2 nM and also inhibits c-Kit. Tanshinone IIA - CAS 568-72-9 Catalog Number: B0084-188817 Molecular Weight: 294.34 Molecular Formula: C19H18O3 Description: Tanshinone IIA under the IUPAC name 166-trimethyl-89-dihydro-7H-naphtho12- g1benzofuran-1011-dione one of the original anthracyclines isolated from Salvia miltiorrhiza inhibits β-amyloid aggregation and protects PC12 cells from β-amyloid-induced apoptosis. slide 14: www.bocsci.com 14 / 33 Aflibercept - CAS 862111-32-8 Catalog Number: B0084-244884 Molecular Weight: 96898.57 Molecular Formula: C4318H6788N1164O1304S32 Description: Aflibercept is a recombinant fusion protein and acts as a VEGF inhibitor. Aflibercept is used for the treatment of wet macular degeneration and metastatic colorectal cancer. PD173074 - CAS 219580-11-7 Catalog Number: B0084-263525 Molecular Weight: 523.682 Molecular Formula: C28H41N7O3 Description: PD173074 is a small-molecule FGFR3-selective tyrosine kinase inhibitor TKI as a therapeutic modality using eight UC cell lines. PD173074 suppressed cell proliferation remarkably in two cell lines namely UM-UC-14 and MGHU3 which expressed mutated FGFR3 protein. Cell cycle analysis revealed the growth inhibitory effect of PD173074 was associated with arrest at G1-S transition in a dose-depending manner. In the mouse xenograft models using subcutaneously transplanted UM-UC-14 and MGHU3 orally administered PD173074 suppressed tumor growth and induced apoptotic changes comparable with the results of our in vitro assay. These findings elucidated the effectiveness of molecular targeted approach for bladder UC harboring FGFR3 mutations and the potential utility to decrease the intravesical recurrence of nonmuscle invasive bladder UC after transurethral surgical resection. R916562 - CAS 1037798-41-6 Catalog Number: B0084-267742 Molecular Weight: 536.09 Molecular Formula: C26H30ClN9S Description: R916562 a diaminotriazole compound is a potential and selective Axl/VEGF-R2 dual inhibitor with IC50s of 136 and 24 nM respectively. R916562 showed activity comparable to the clinically approved tyrosine kinase inhibitor Sunitinib in mouse tumor xenograft models and the corneal micropocket angiogenesis model. Anlotinib Dihydrochloride - CAS 1360460-82-7 Catalog Number: B0084-267743 Molecular Weight: 480.36 Molecular Formula: C23H22FN3O3.2ClH Description: Anlotinib Dihydrochloride is a novel multi-target tyrosine kinase inhibitor with potential antineoplastic and anti-angiogenic activities which was designed to primarily inhibit VEGFR2/3 FGFR1-4 PDGFR α/ β c-Kit and Ret. slide 15: www.bocsci.com 15 / 33 BFH772 - CAS 890128-81-1 Catalog Number: B0084-267744 Molecular Weight: 439.4 Molecular Formula: C23H16F3N3O3 Description: BFH772 a structure analogue of BAW2881 was highly effective at targeting VEGFR2 kinase with an IC50 value of 3 nM however lost 500-fold potency on FLK-1 FLT-1 and FLT-4. BFH772 inhibits the ligand induced autophosphorylation of RET PDGFR and KIT kinases with IC50 values ranging between 30 and 160 nM. Ningetinib - CAS 1394820-69-9 Catalog Number: B0084-267745 Molecular Weight: 728.79 Molecular Formula: C31H29FN4O5 Description: Ningetinib is a potent orally bioavailable small molecule tyrosine kinase inhibitor TKI with IC50s of 6.7 1.9 and 1.0 nM for c-Met VEGFR2 and Axl respectively. In vivo ningetinib 20 mg/kg inhibits tumor growth in MKN45 Caki-1 NCI-H441 Huh-7 U87MG and MDA-MB-231 mouse xenograft models by 53-97. Pz-1 - CAS 1800505-64-9 Catalog Number: B0084-267746 Molecular Weight: 454.52 Molecular Formula: C26H26N6O2 Description: Pz-1 is a cell-permeable non-cytotoxic up to 0.1 μM and 6 days NIH/3T3 cells and highly potent RET and VEGFR2 inhibitor with IC50s of less than 1 nM for both wild type kinases. BMS-794833 - CAS 1174046-72-0 Catalog Number: B0084-286366 Molecular Weight: 468.845 Molecular Formula: C23H15ClF2N4O3 Description: BMS-794833 is a potent ATP competitive inhibitor of Met/VEGFR2 with IC50 of 1.7 nM/15 nM. slide 16: www.bocsci.com 16 / 33 KRN633 - CAS 286370-15-8 Catalog Number: B0084-286440 Molecular Weight: 416.86 Molecular Formula: C20H21ClN4O4 Description: KRN633 is a potent and selective VEGFR inhibitor. which inhibits tyrosine phosphorylation of VEGFR-2 IC50 1.16 nmol/L in human umbilical vein endothelial cells. Selectivity profiling with recombinant tyrosine kinases showed that KRN633 is highly selective for VEGFR-1 -2 and -3. KRN633 inhibits tumor growth in several in vivo tumor xenograft models with diverse tissue origins including lung colon and prostate in athymic mice and rats. KRN633 also causes the regression of some well-established tumors and those that had regrown after the cessation of treatment. KRN633 was well tolerated and had no significant effects on body weight or the general health of the animals. KRN633 might be useful in the treatment of solid tumors and other diseases that depend on pathologic angiogenesis. LY2784544 - CAS 1229236-86-5 Catalog Number: B0084-286443 Molecular Weight: 469.949 Molecular Formula: C23H25ClFN7O Description: Gandotinib is a potent and selective JAK inhibitor which effectively inhibited JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells IC5020 and 55 nM respectively. RAF265 - CAS 927880-90-8 Catalog Number: B0084-286688 Molecular Weight: 518.41 Molecular Formula: C24H16F6N6O Description: RAF265 is a potent selective inhibitor of C-Raf/B-Raf/B-Raf V600E with IC50 of 3-60 nM and exhibits potent inhibition on VEGFR2 phosphorylation with EC50 of 30 nM. Cabozantinib - CAS 849217-68-1 Catalog Number: B0084-307706 Molecular Weight: 501.51 Molecular Formula: C28H24FN3O5 Description: Cabozantinib is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c- Met Ret Kit Flt-1/3/4 Tie2 and AXL with IC50 of 1.3 nM 4 nM 4.6 nM 12 nM/11.3 nM/6 nM 14.3 nM and 7 nM respectively. slide 17: www.bocsci.com 17 / 33 SU5408 - CAS 15966-93-5 Catalog Number: B0084-312027 Molecular Weight: 310.35 Molecular Formula: C18H18N2O3 Description: A potent selective and cell-permeable inhibitor of VEGFR2 kinaseIC50 70 nM with little or no effect against receptors for platelet-derived growth factor epidermal growth factor or insulin-like growth factor IC50 100 µM. SU11652 - CAS 326914-10-7 Catalog Number: B0084-313239 Molecular Weight: 414.93 Molecular Formula: C22H27ClN4O2 Description: SU11652 is a cell-permeable and sunitinib-like inhibitor of tyrosine kinase receptor RTK and angiogenesis with antineoplastic property. It selectively inhibits PDGFR- β VEGFR2 FGFR1 FLT3 IC50 values of 3 27 170 and 1.5 nM respectively and Kit family members IC5010- 500 nM. Vatalanib - CAS 212141-54-3 Catalog Number: B0084-341508 Molecular Weight: 346.81 Molecular Formula: C20H15ClN4 Description: Vatalanib also called as PTK 787 or CGP 797870 is a small molecule that interacts reversibly and competitively at the ATP-binding site of the receptor tyrosine kinase domain to inhibit autophosphorylation. It targets all known VEGFR tyrosine kinases th Vandetanib - CAS 443913-73-3 Catalog Number: B0084-344311 Molecular Weight: 475.35 Molecular Formula: C22H24BrFN4O2 Description: Vandetanib ZD6474 is a potent inhibitor of VEGFR2 with IC50 of 40 nM. slide 18: www.bocsci.com 18 / 33 Tyrphostin 9 - CAS 10537-47-0 Catalog Number: B0084-358320 Molecular Weight: 282.38 Molecular Formula: C18H22N2O Description: Tyrphostin 9 is firstly designed as an EGFR inhibitor with IC50 of 460 μM but is also found to be more potent to PDGFR with IC50 of 0.5 μM. PP121 - CAS 1092788-83-4 Catalog Number: B0084-358783 Molecular Weight: 319.372 Molecular Formula: C17H17N7 Description: PP121 is a multitargeted dual receptor tyrosine kinases inhibitor. PP121 blocks the proliferation of tumor cells by direct inhibition of oncogenic tyrosine kinases and phosphatidylinositol-3-OH kinases. DMH4 - CAS 515880-75-8 Catalog Number: B0084-373940 Molecular Weight: 400.47 Molecular Formula: C24H24N4O2 Description: DMH4 is a selective VEGFR-2 inhibitor IC50 values are 161 3558 8038 and 30000 nM for VEGFR-2 BMPR-I AMPK and TGF βR-I respectively with antiangiogenic activity in vitro and in vivo. BMS-6690514 - CAS 859853-30-8 Catalog Number: B0084-385098 Molecular Weight: 368.441 Molecular Formula: C19H24N6O2 Description: BMS-690514 is a potent inhibitor of human epidermal growth factor receptor HER 1 EGFR 2 and 4 and vascular endothelial growth factor receptors VEGFR 1-3. BMS-690514 is currently under investigation as an oral agent for the treatment of solid tumors. The preclinical ADME properties of BMS-690514 suggest good oral bioavailability in humans and metabolism by multiple pathways including oxidation and glucuronidation. slide 19: www.bocsci.com 19 / 33 Orantinib - CAS 252916-29-3 Catalog Number: B0084-409435 Molecular Weight: 310.353 Molecular Formula: C18H18N2O3 Description: TSU-68 SU6668 Orantinib is a novel multiple receptor tyrosine kinase inhibitor with IC50 of 2.1 μM 8 nM and 1.2 μM for VEGF-R1 PDGF-R β and FGF-R1 respectively has greatest potency against PDGFR autophosphorylation. Tivozanib - CAS 475108-18-0 Catalog Number: B0084-413727 Molecular Weight: 454.86306 Molecular Formula: C22H19ClN4O5 Description: Tivozanib is an orally bioavailable inhibitor of vascular endothelial growth factor receptors VEGFRs 1 2 and 3 with potential antiangiogenic and antineoplastic activities. Tivozanib binds to and inhibits VEGFRs 1 2 and 3 which may result in the inhibition of endothelial cell migration and proliferation inhibition of tumor angiogenesis and tumor cell death. VEGFR tyrosine kinases frequently overexpressed by a variety of tumor cell types play a key role in angiogenesis. Check for active clinical trials or closed clinical trials using this agent. ZM306416 - CAS 690206-97-4 Catalog Number: B0084-418967 Molecular Weight: 333.74 Molecular Formula: C16H13ClFN3O2 Description: ZM306416 is a vascular endothelial growth factor receptor VEGFR antagonist. PF-03814735 - CAS 942487-16-3 Catalog Number: B0084-428251 Molecular Weight: 474.48 Molecular Formula: C23H25F3N6O2 Description: PF-03814735 is an orally bioavailable ATP-competitive reversible small-molecule Aurora kinase inhibitor with potential antineoplastic activity. Aurora kinase inhibitor PF-03814735 binds to and inhibits Aurora kinases A and B which may result in the inhibition of cellular division and proliferation in tumor cells that overexpress these kinases. Aurora kinases are serine- threonine kinases that play essential roles in mitotic checkpoint control during mitosis. slide 20: www.bocsci.com 20 / 33 SU1498 - CAS 168835-82-3 Catalog Number: B0084-428540 Molecular Weight: 390.52 Molecular Formula: C25H30N2O2 Description: SU1498 is a selective inhibitor of the receptor tyrosine kinase VEGF receptor 2 VEGFR2 aka FLK1 IC50 700 nM and inhibits Flk-1 with an IC50 of value of 700 nM. TG 100572 - CAS 867334-05-2 Catalog Number: B0084-429717 Molecular Weight: 475.97 Molecular Formula: C26H26ClN5O2 Description: TG 100572 is a multi-targeted kinase inhibitor that inhibits select growth factor receptor tyrosine kinases and Src familt kinases. TG 100801 - CAS 867331-82-6 Catalog Number: B0084-429718 Molecular Weight: 580.08 Molecular Formula: C33H30ClN5O3 Description: TG 100801 is the prodrug of TG 100572 which is a multi-targeted kinase inhibitor that inhibit select growth factor receptor tyrosine kinases and Src familt kinases. It is currently in a clinical trial as a first in class VEGFr2 targeting topically applied compound for the treatment of AMD. It is a new drug that inhibits ocular angiogenesis vascular leak and inflammation in laboratory studies. CGP60474 - CAS 164658-13-3 Catalog Number: B0084-430557 Molecular Weight: 355.82 Molecular Formula: C18H18ClN5O Description: CGP60474 is a promising inhibitor of PKC with a high degree of selectivity versus other serine/threonine and tyrosine kinases and show competitive kinetics relative to ATP. slide 21: www.bocsci.com 21 / 33 SU14813 - CAS 627908-92-3 Catalog Number: B0084-431172 Molecular Weight: 442.491 Molecular Formula: C23H27FN4O4 Description: SU14813 is an oral multitargeted tyrosine kinase inhibitor TKI targeting vascular endothelial growth factor receptors VEGFR platelet-derived growth factor receptors PDGFR KIT and fms-like tyrosine kinase 3 FLT-3 1. SU14813 was developed as a next-generation TKI agent following sunitinib SU11248 designed to demonstrate optimized pharmacokinetic PK and tolerability profiles. SU14813 demonstrated broad and potent antitumor activity equivalent to that of sunitinib which resulted in tumor regression growth arrest growth delay and prolonged survival in established xenograft cancer models in mice. Toceranib - CAS 356068-94-5 Catalog Number: B0084-455463 Molecular Weight: 396.46 Molecular Formula: C22H25FN4O2 Description: Toceranib CAS 356068-94-5 is a potent ATP-competitive PDGFR and VEGFR inhibitor Ki 5 and 6 nM respectively inhibits phosphorylation of c-Kit and suppresses the growth of mast cell lines expressing mutant Kit inducing cell cycle arrest and apoptosis. Also inhibits FGFR1 Ki 0.5 μM. Effective in vivo. TG 100801 Hydrochloride - CAS 1018069-81-2 Catalog Number: B0084-456447 Molecular Weight: 616.54 Molecular Formula: C33H31Cl2N5O3 Description: TG 100801 is the prodrug of TG 100572 which is a multi-targeted kinase inhibitor that inhibit select growth factor receptor tyrosine kinases and Src familt kinases with IC50 values of 2/7/2/1/0.5 nM or VEGFR1/VEGFR2/FGFR1/Src/Fy Lucitanib - CAS 1058137-23-7 Catalog Number: B0084-456732 Molecular Weight: 443.503 Molecular Formula: C26H25N3O4 Description: Lucitanib also known as E-3810 is a novel dual inhibitor targeting human vascular endothelial growth factor receptors VEGFRs and fibroblast growth factor receptors FGFRs with antiangiogenic activity. VEGFR/FGFR dual kinase inhibitor E-3810 inhibits VEGFR-1 -2 -3 and FGFR-1 -2 kinases in the nM range which may result in the inhibition of tumor angiogenesis and tumor cell proliferation and the induction of tumor cell death. Both VEGFRs and FGFRs belong to the family of receptor tyrosine kinases that may be upregulated in various tumor cell types. slide 22: www.bocsci.com 22 / 33 Cabozantinib malate XL184 - CAS 1140909-48-3 Catalog Number: B0084-457054 Molecular Weight: 635.59 Molecular Formula: C28H24FN3O5.C4H6O5 Description: Cabozantinib malate is the malate of Cabozantinib a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met Ret Kit Flt-1/3/4 Tie2 and AXL with IC50 of 1.3 nM 4 nM 4.6 nM 12 nM/11.3 nM/6 nM 14.3 nM and 7 nM respectively. EG00229 - CAS 1210945-69-9 Catalog Number: B0084-457636 Molecular Weight: 611.6 Molecular Formula: C19H20F3N7O7S3 Description: EG00229 is a small molecule inhibitor of neuropilin-1Nrp1 with an IC50 of 3 μM. EG00229 has been reported to inhibit VEGF-A binding to PAE/NRP1 in the Nrp1and bt-VEGF-A binding to purified Nrp1 b1 domain in a cell-free assay with an IC50 value of 8 μM and 3 μM respectively. In addition EG00229 has also shown the inhibition of VEGF-A binding to VEGFR2 VEGFR1 and Nrp1 in human umbilical vein endothelial cells HUVECs in a dose-dependent manner with an IC50 value of 23 μM 1. Besides EG00229 has been revealed to prevent tuftsin binding to the Nrp1 which is at the cell surface. Moreover EG00229 has been noted to suppress the anti- inflammatory M2 shift in microglia induced by tuftsin and thus potently prevent tuftsin’s action. Apatinib - CAS 1218779-75-9 Catalog Number: B0084-457664 Molecular Weight: 493.58 Molecular Formula: C25H27N5O4S Description: Apatinib mesylate is an orally bioavailable small-molecule receptor tyrosine kinase inhibitor with potential antiangiogenic and antineoplastic activities. Apatinib selectively binds to and inhibits vascular endothelial growth factor receptor 2 which may inhibit VEGF-stimulated endothelial cell migration and proliferation and decrease tumor microvessel density. In addition this agent mildly inhibits c-Kit and c-SRC tyrosine kinases. ENMD-2076 L-+-Tartaric acid - CAS 1291074-87-7 Catalog Number: B0084-457865 Molecular Weight: 525.56 Molecular Formula: C25H31N7O6 Description: ENMD-2076 L-+-Tartaric acid is the tartaric acid of ENMD-2076 selective activity against Aurora A and Flt3 with IC50 of 14 nM and 1.86 nM 25-fold more selective for Aurora A than Aurora B and less potent to VEGFR2/KDR and VEGFR3 FGFR1 and FGFR2 slide 23: www.bocsci.com 23 / 33 XL-647 - CAS 781613-23-8 Catalog Number: B0084-459630 Molecular Weight: 491.39 Molecular Formula: C24H25Cl2FN4O2 Description: XL647 is an orally bioavailable small-molecule receptor tyrosine kinase inhibitor with potential antineoplastic activity. It inhibits EGFR HER2 VEGFR and EphB4 kinase. Regorafenib Hydrochloride - CAS 835621-07-3 Catalog Number: B0084-459775 Molecular Weight: 519.28 Molecular Formula: C21H16Cl2F4N4O3 Description: Regorafenib Hydrochloride is a multi-target inhibitor for VEGFR1 VEGFR2 VEGFR3 PDGFR β Kit RET and Raf-1. SU14813 maleate - CAS 849643-15-8 Catalog Number: B0084-459836 Molecular Weight: 558.56 Molecular Formula: C27H31FN4O8 Description: SU14813 maleate is an oral multitargeted tyrosine kinase inhibitor TKI targeting vascular endothelial growth factor receptors VEGFR platelet-derived growth factor receptors PDGFR Kit and fms-like tyrosine kinase 3 FLT-3. It was developed as a next-generation TKI agent following sunitinib SU11248 designed to demonstrate optimized pharmacokinetic PK and tolerability profiles. It demonstrated broad and potent antitumor activity equivalent to that of sunitinib which resulted in tumor regression growth arrest growth delay and prolonged survival in established xenograft cancer models in mice. Cediranib maleate - CAS 857036-77-2 Catalog Number: B0084-459903 Molecular Weight: 566.56 Molecular Formula: C29H31FN4O7 Description: Cediranib maleate is a highly potent VEGFR KDR inhibitor with IC50 of 1 nM. It also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM. It inhibits VEGF-stimulated proliferation with IC50 of 0.4 nM in vitro. It suppresses PDGF-AA with IC50 of 0.04 μM in MG63 cell lines. It even suppresses tubule sprouting at subnanomolar concentrations and inhibits VEGF-induced angiogenesis in vivo. It causes hypertrophy in bone growth plate and prevents luteal development in ovary. It shows broad spectrum activity in human tumor models at doses that are well tolerated. It causes regression of vascular tissues in human lung tumor xenografts. slide 24: www.bocsci.com 24 / 33 TG 100572 Hydrochloride - CAS 867331-64-4 Catalog Number: B0084-460028 Molecular Weight: 512.43 Molecular Formula: C26H27Cl2N5O2 Description: TG 100572 is a multi-targeted kinase inhibitor that inhibit select growth factor receptor tyrosine kinases and Src familt kinases for VEGFR1/VEGFR2/FGFR1/Src/Fyn kianse. ZK-261991 - CAS 886563-25-3 Catalog Number: B0084-460234 Molecular Weight: 443.5 Molecular Formula: C24H25N7O2 Description: ZK-261991 is an orally active VEGFR tyrosine kinase inhibitor with an IC50 of 5 nM for VEGFR2. The high efficacy including tumour regression in established tumours combined with its low toxicity recommends ZK 261991 for development as a drug for the therapy of solid tumours also in combination with other chemotherapeutics. Golvatinib - CAS 928037-13-2 Catalog Number: B0084-460626 Molecular Weight: 633.701 Molecular Formula: C33H37F2N7O4 Description: golvatinib also known as E7050 is an orally bioavailable dual kinase inhibitor of c- Met hepatocyte growth factor receptor and VEGFR-2 vascular endothelial growth factor receptor-2 tyrosine kinases with potential antineoplastic activity. c-Met/VEGFR kinase inhibitor E7050 binds to and inhibits the activities of both c-Met and VEGFR-2 which may inhibit tumor cell growth and survival of tumor cells that overexpress these receptor tyrosine kinases. c-Met and VEGFR-2 are upregulated in a variety of various tumor cell types and play important roles in tumor cell growth migration and angiogenesis. Axitinib - CAS 319460-85-0 Catalog Number: B0084-461979 Molecular Weight: 386.47 Molecular Formula: C22H18N4OS Description: axitinib is an orally bioavailable tyrosine kinase inhibitor. Axitinib inhibits the proangiogenic cytokines vascular endothelial growth factor VEGF and platelet-derived growth factor receptor PDGF thereby exerting an anti-angiogenic effect. slide 25: www.bocsci.com 25 / 33 XL999 - CAS 705946-27-6 Catalog Number: B0084-462245 Molecular Weight: 445.532 Molecular Formula: C26H28FN5O Description: XL999 a Spectrum Selective Kinase InhibitorTM SSKIs is a potent inhibitor of key RTKs implicated in the development and maintenance of tumor vasculature and in the proliferation of some tumor cells. It inhibits the FGFR VEGFR and PDGFR RTKs and exhibited excellent activity in target-specific cellular functional assays. In addition XL999 is a potent inhibitor of FLT3 an important driver of leukemia cell proliferation in some patients with acute myelogenous leukemia AML. In several preclinical models of human tumors including breast lung colon and prostate cancer XL999 demonstrated potent inhibition of tumor growth and also caused regression of large well-established tumors. Phase I studies of XL999 established a maximum tolerated dose and showed evidence of tumor responses. JI-101 - CAS 900573-88-8 Catalog Number: B0084-462546 Molecular Weight: 466.339 Molecular Formula: C22H20BrN5O2 Description: JI-101 is an orally active inhibitor of vascular endothelial growth factor receptor 2 VEGFR2 platelet-derived growth factor receptor beta PDGFRb and the ephrin B4 receptor B4 EphB4 with potential antiangiogenic and antineoplastic activities. Angiogenesis inhibitor JI-101 binds to and inhibits VEGFR2 PDGFRb and EphB4 which may inhibit tumor angiogenesis and so cellular proliferation in tumor cells overexpressing VEGFR2 PDGFRb and EphB4. The receptor tyrosine kinases VEGFR2 PDGFRb and EphB4 may be overexpressed in a number of different cancer cell types and may play crucial roles in tumor angiogenesis. SKLB610 - CAS 1125780-41-7 Catalog Number: B0084-462581 Molecular Weight: 415.372 Molecular Formula: C21H16F3N3O3 Description: SKLB610 is a VEGFR inhibitor that potently suppresses human tumor angiogenesis. SKLB610 inhibited angiogenesis-related tyrosine kinase VEGFR2 fibroblast growth factor receptor 2 FGFR2 and platelet-derived growth factor receptor PDGFR at rate of 97 65 and 55 respectively at concentration of 10 μM in biochemical kinase assays. SKLB610 exhibited its antitumor activity as a multi-targeted inhibitor with more potent inhibition of VEGFR2 activity. Its potential to be a candidate of anticancer agent is worth being further investigated. slide 26: www.bocsci.com 26 / 33 SKLB1002 - CAS 1225451-84-2 Catalog Number: B0084-462582 Molecular Weight: 320.39 Molecular Formula: C13H12N4O2S2 Description: SKLB1002 is a new potent VEGFR2 inhibitor which could significantly inhibit HUVEC proliferation migration invasion and tube formation. In vivo zebrafish model experiments showed that SKLB1002 remarkably blocked the formation of intersegmental vessels in zebrafish embryos. SKLB1002 inhibits angiogenesis and may be a potential drug candidate in anticancer therapy. Ilorasertib - CAS 1227939-82-3 Catalog Number: B0084-462639 Molecular Weight: 488.541 Molecular Formula: C25H21FN6O2S Description: Ilorasertib also known as ABT-348 is a novel potent and orally bioavailable inhibitor of the Aurora kinases as well as the VEGF and PDGF families of receptor tyrosine kinases and is currently in Phase I clinical trials. ABT-348 has nanomolar potency IC50 for inhibiting binding and cellular auto-phosphorylation of Aurora B 7 and 13 nM C 1 and 13 nM and A 120 and 189 nM. These results provide the rationale for clinical assessment of ABT-348 as a therapeutic agent in the treatment of cancer. R1530 - CAS 882531-87-5 Catalog Number: B0084-462772 Molecular Weight: 356.78136 Molecular Formula: C18H14ClFN4O Description: R1530 is a pyrazolobenzodiazepine small molecule with potential antiangiogenesis and antineoplastic activities. R1530 is also a mitosis-angiogenesis inhibitor MAI that inhibits multiple receptor tyrosine kinases involved in angiogenesis such as vascular endothelial growth factor receptor VEGFR-1 -2 -3 platelet-derived growth factor receptor PDGFR beta‚ FMS-like tyrosine kinase Flt-3 and fibroblast growth factor receptor FGFR -1 -2. In addition this agents exhibits anti-proliferative activity by initiating mitotic arrest and inducing apoptosis. slide 27: www.bocsci.com 27 / 33 TAK-593 - CAS 1005780-62-0 Catalog Number: B0084-462796 Molecular Weight: 445.483 Molecular Formula: C23H23N7O3 Description: TAK-593 is an oral formulation containing a small-molecule receptor tyrosine kinase inhibitor of both vascular endothelial growth factor receptor VEGFR and platelet-derived growth factor receptor PDGFR with potential antineoplastic activity. TAK-593 selectively binds to and inhibits VEGFR and PDGFR which may result in the inhibition of angiogenesis and tumor cell proliferation. Check for active clinical trials or closed clinical trials using this agent. Altiratinib - CAS 1345847-93-9 Catalog Number: B0084-463181 Molecular Weight: 510.46 Molecular Formula: C26H21F3N4O4 Description: Altiratinib also known as DCC-270 DP-5164 is an oral selective and highly potent inhibitor of MET TIE2 VEGFR2 and TRK kinases with potential anticancer activity. DCC-2701 effectively reduces tumor burden in vivo and blocks c-MET pTyr1349-mediated signaling cell growth and migration as compared with a HGF antagonist in vitro. Importantly DCC-2701s anti- proliferative activity was dependent on c-MET activation induced by stromal human fibroblasts and to a lesser extent exogenous HGF. DCC-2701 may be superior to HGF antagonists that are in clinical trials and that pTyr1349 levels might be a good indicator of c-MET activation and likely response to targeted therapy as a result of signals from the microenvironment. 24-Pyrimidinediamine with linker - CAS 1430089-64-7 Catalog Number: B0084-463236 Molecular Weight: 364.45 Molecular Formula: C19H24N8 Description: 24-Pyrimidinediamine with linker is a patent compound in WO2013055780A1 Page 71 multikinase inhibitor and has a -NH2 terminal linker for further synthesis. slide 28: www.bocsci.com 28 / 33 WHI-P180 hydrochloride - CAS 153437-55-9 Catalog Number: B0084-463265 Molecular Weight: 333.77 Molecular Formula: C16H16ClN3O3 Description: WHI-P180 moderately inhibited ABCG2 function exhibiting weak phototoxicity. The elimination half-life of WHI-P180 in CD-1 mice BALB/ c mice following i.v. i.p. or p.o. administration was less than 10 min. Systemic clearance of WHI-P180 was 6742 mL/h/kg in CD-I mice and 8188 mL/h/kg in BALB/c mice. Notably WHI-P180 when administered in two consecutive nontoxic i.p. bolus doses of 25 mg/kg inhibited IgE/antigen-induced vascular hyperpermeability in a well-characterized murine model of passive cutaneous anaphylaxis. Vandetanib hydrochloride - CAS 524722-52-9 Catalog Number: B0084-463282 Molecular Weight: 511.81 Molecular Formula: C22H25BrClFN4O2 Description: Vandetanib hydrochloride is an anti-cancer drug that is used for the treatment of certain tumours of thethyroid gland. It acts as a kinase inhibitor of a number of cell receptors mainly the vascular endothelial growth factor receptor VEGFR the epidermal growth factor receptor EGFR and the RET-tyrosine kinase. AST 487 - CAS 630124-46-8 Catalog Number: B0084-463295 Molecular Weight: 529.56 Molecular Formula: C26H30F3N7O2 Description: AST487 is a Ret kinase inhibitor/FLT3 inhibitor which displays high selectivity and potency toward FLT3 as a molecular target and which could potentially be used to override drug resistance in AML. It induced a dose-dependent growth inhibition of xenografts of NIH3T3 cells expressing oncogenic RET and of the MTC cell line TT in nude mice.It also inhibited calcitonin gene expression in vitro in TT cells in part through decreased gene transcription. SAR131675 - CAS 1433953-83-3 Catalog Number: B0084-463427 Molecular Weight: 358.39 Molecular Formula: C18H22N4O4 Description: SAR131675 dose dependently inhibits the proliferation of primary human lymphatic cells induced by the VEGFR-3 ligands VEGFC and VEGFD with an IC50 of about 20 nM. slide 29: www.bocsci.com 29 / 33 Regorafenib monohydrate - CAS 1019206-88-2 Catalog Number: B0084-463493 Molecular Weight: 500.83 Molecular Formula: C21H17ClF4N4O4 Description: Regorafenib monohydrate is a multitargetedinhibitor of tyrosine kinase with IC50 values of 13nM 4.2nM 46nM 2.5nM 28nM 19nM 202nM 22nM 7nM 1.5nM and 311nM respectively for VEGFR-1 mVEGFR-2 mVEGFR-3 Raf-1 BRAF WT BRAFV600E FGFR-1 PDGFR- β c-KIT RET and TIE2. ZM323881 hydrochloride - CAS 193000-39-4 Catalog Number: B0084-463579 Molecular Weight: 411.86 Molecular Formula: C22H19ClFN3O2 Description: Potent and selective inhibitor of VEGFR2 IC50: 2 nM for VEGFR2 vs 50 mM for VEGFR1 respectively ZM323881 - CAS 193001-14-8 Catalog Number: B0084-463580 Molecular Weight: 375.4 Molecular Formula: C22H18FN3O2 Description: ZM323881 inhibits VEGF-A EGF and bFEF induced HUVEC cell proliferation with IC50 of 8 nM 1.9 μM and 1.6 μM respectively. ZM323881 10 nM abolishes VEGF-A-mediated increases in vascular permeability in perfused mesenteric microvessels in male leopard. ZM323881 10 nM blocks the increase in intensity of the VEGF-R2 band in the lung of male leopard frogs. M323881 1 μM blocks activation of extracellular regulated-kinase p38 Akt and endothelial nitric oxide synthetase eNOS by VEGF but did not inhibit p38 activation by the VEGFR-1-specific ligand placental growth factor PIGF in human aortic endothelial cells HAECs. ZM323881 1 μM also perturbes VEGF-induced membrane extension cell migration and tube formation by HAECs. ZM323881 1 μM reverses VEGF-stimulated phosphorylation of CrkII and its Src homology 2 SH2- binding protein p130Cas which are known to play a pivotal role in regulating endothelial cell migration. ZM323881 10 nM completely blocks VEGF-induced VEGF promoter activity in SCC-9 cells. ZM323881 10 nM blocks VEGF stimulated Hif-1 α protein accumulation in SCC-9 cells. ZM323881 10 nM blocks VEGF-induced Rac1 activation at 30 min in HUVECs. ZM323881 10 nM prevents Vav2 tyrosine phosphorylation in response to VEGF in HUVECs. slide 30: www.bocsci.com 30 / 33 Vandetanib trifluoroacetate - CAS 338992-53-3 Catalog Number: B0084-463630 Molecular Weight: 589.38 Molecular Formula: C24H25BrF4N4O4 Description: Vandetanib is an anti-cancer drug that is used for the treatment of certain tumours of thethyroid gland. It acts as a kinase inhibitor of a number of cell receptors mainly the vascular endothelial growth factor receptor VEGFR the epidermal growth factor receptor EGFR and the RET-tyrosine kinase. AZD2932 - CAS 883986-34-3 Catalog Number: B0084-463669 Molecular Weight: 447.49 Molecular Formula: C24H25N5O4 Description: AZD2932 is a new quinazoline ether inhibitor and is a high affinity inhibitor of VEFGR- 2 and PDGFR. It has a balanced 1:1 ratio of activity vs both VEGFR-2 and PDGFR β. It is also active on c-Kit and FLT3 with good selectivity on a panel of kinases. ACTB-1003 - CAS 939805-30-8 Catalog Number: B0084-463692 Molecular Weight: 591.53 Molecular Formula: C27H26F5N7O3 Description: ACTB-1003 is an oral kinase inhibitor with multiple modes of action targeting cancer mutations via FGFR inhibition FGFR1 angiogenesis through inhibition of VEGFR2 Tie-2 and induces apoptosis likely by targeting RSK and p70S6K. It is highly active with dose-dependent tumor growth inhibition in cell lines with FGFR genetic alterations - OPM2 human multiple myeloma and the murine leukemia Ba/F3-TEL-FGFR1. Fruquintinib - CAS 1194506-26-7 Catalog Number: B0084-470819 Molecular Weight: 393.39 Molecular Formula: C21H19N3O5 Description: Fruquintinib also known as HMPL-013 is an orally available small molecule inhibitor of vascular endothelial growth factor receptors VEGFRs with potential anti-angiogenic and antineoplastic activities. slide 31: www.bocsci.com 31 / 33 Anlotinib - CAS 1058156-90-3 Catalog Number: B0084-474328 Molecular Weight: 407.44 Molecular Formula: C23H22FN3O3 Description: Anlotibib is a multi-targetes kinase inhibitor of receptor tyrosine and could effectively resist the formation of new angiogenesis and is under Phase III trial for exploring the effectiveness and safety of andvanced non-small cell lung cancer by Chiatai T SCR-1481B1 - CAS 1174161-86-4 Catalog Number: B0084-474369 Molecular Weight: 699.98 Molecular Formula: C28H29ClF2N5O10P Description: SCR-1481B1 also known as c-Met inhibitor 2 is an effective inhibitor of MET kinase so that probably has anti-tumor activity. It is also found to be an inhibitor of VEGFR. IC50: 1.7 nM for MET kinase. Flumatinib - CAS 895519-90-1 Catalog Number: B0084-474894 Molecular Weight: 562.59 Molecular Formula: C29H29F3N8O Description: Flumatinib is a multi-kinase inhibitor of c-Abl PDGFR β and c-Kit with IC50 values of 1.2 nM 307.6 nM and 2662 nM respectively. It can predominantly inhibit the autophosphorylation of Bcr-Abl in K562 cell in vitro. It can inhibit the phosphorylation of c-Kit in Mo7e cell and the phosphorylation of PDGFR in Swiss3T3 cell in higher concentration. It has no or little effect on other tyrosine kinase including EGFR 、KDR 、c-Src andHER2. It can reduce the expression of C- MYC HIF-1 α and VEGF in U266 cell line in a time- and dose-dependent manners. It effectively overcame the drug resistance of certain KIT mutants with activation loop mutations. It was developed by Jiangsu Hansoh Pharmaceutical Co. Ltd. and is currently in Phase III clinical trials in China for the treatment of chronic myelogenous leukemia CML. slide 32: www.bocsci.com 32 / 33 TAS-115 - CAS 1190836-34-0 Catalog Number: B0084-475134 Molecular Weight: 518.56 Molecular Formula: C27H23FN4O4S Description: This active molecular is a c-MET and VEGFR inhibitor which is selective and specific in vitro. In vivo studies TAS-115 suppressed the progression of MET-inactivated tumor completely through blocking angiogenesis without toxicity and it also induced marked tumor shrinkage and prolonged survival in animal model. In Dec 2013 Phase-I development was ongoing in Japan. In Dec 2014 Taiho Pharmaceutical completed a phase I trial for Solid tumours in Japan. In Apr 2016 preclinical data was presented. ARQ 736 disodium salt - CAS 1228237-57-7 Catalog Number: B0084-475181 Molecular Weight: 674.54 Molecular Formula: C25H25N8Na2O8PS Description: This active molecular is a Proto oncogene protein b raf and Vascular endothelial growth factor a inhibitor originated by ArQule. ARQ 736 is effective in killing cancer cell lines that harboring at least one mutated b raf allele. The b raf protein is really a very important signaling molecule in the MAPK mitogen activated protein kinase signaling pathway and it relates to pathogenesis of variety kinds of cancer. In Mar 2014 Phase-I for Solid tumours late-stage disease was discontinued in USA. BRN-103 - CAS 1346265-80-2 Catalog Number: B0084-475331 Molecular Weight: 420.93 Molecular Formula: C24H25ClN4O Description: BRN-103 can suppress the phosphorylation of vascular endothelial growth factor VEGF receptor 2. It can also inhibit the activations of AKT and eNOS. These results show that BRN-103 inhibits VEGF-mediated angiogenesis signaling in human endothelial cells. JNJ 17029259 - CAS 314267-57-7 Catalog Number: B0084-475639 Molecular Weight: 442.56 Molecular Formula: C26H30N6O Description: JNJ 17029259 is an selective nanomolar inhibitors of the vascular endothelial growth factor receptor-2 VEGF-R2 blocks VEGF-stimulated mitogen-activated protein kinase signaling proliferation/migration. slide 33: www.bocsci.com 33 / 33 AG28262 - CAS 638216-89-4 Catalog Number: B0084-476068 Molecular Weight: 434.53 Molecular Formula: C22H18N4O2S2 Description: AG28262 is a bio-active chemical compound. It is a VEFG-r2 inhibitor and could cause an increase in serum ALT due in part to both gene up-regulation. BAW2881 - CAS 861875-60-7 Catalog Number: B0084-476680 Molecular Weight: 424.38 Molecular Formula: C22H15F3N4O2 Description: BAW 2881 is a VEGFR vascular endothelial growth factor receptor inhibitor IC50 0.82 0.037 and 0.42 µM for VEGFR1 2 and 3 respectively.It can inhibit proliferation migration and tube formation by human umbilical vein endothelial cells and lymphatic endothelial cells in vitro.