Antitumor agent-70 (compound 8b) has anti-tumor activity and can induce cell apoptosis. Antitumor agent-70 inhibits multiple myeloma with an IC50 value of 0.12 μM. Antitumor agent-70 is a potential multi-targeted kinase inhibitor especially for c-Kit[1].
Imatinib is a tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC50=100 nM) tyrosine kinases.
Imatinib Mesylate is a tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC50=100 nM) tyrosine kinases.
SU11652 is a potent receptor tyrosine kinase (RTK) inhibitor. SU11652 also inhibits several members of the split kinase family of RTKs, including VEGFR, FGFR, PDGFR, and Kit. SU11652 can be uesd for spontaneous cancers expressing Kit mutations research[1].
Elenestinib (BLU-263) is a potent and orally active tyrosine kinase inhibitor. Elenestinib has the potential for the research of systemic mastocytosis (SM)[1].
AZD3229 is a potent pan-KIT mutant inhibitor for the treatment of gastrointestinal stromal tumors.
Elenestinib phosphate (BLU-263 phosphate) is a potent and orally active tyrosine kinase inhibitor. Elenestinib phosphate has the potential for the research of systemic mastocytosis (SM)[1].
CHMFL-ABL/KIT-155 (CHMFL-ABL-KIT-155; compound 34) is a highly potent and orally active type II ABL/c-KIT dual kinase inhibitor (IC50s of 46 nM and 75 nM, respectively), and it also presents significant inhibitory activities to BLK (IC50=81 nM), CSF1R (IC50=227 nM), DDR1 (IC50=116 nM), DDR2 (IC50=325 nM), LCK (IC50=12 nM) and PDGFRβ (IC50=80 nM) kinases. CHMFL-ABL/KIT-155 (CHMFL-ABL-KIT-155) arrests cell cycle progression and induces apoptosis[1].
Imatinib D4 (STI571 D4) is a deuterium labeled Imatinib (STI571). Imatinib is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, v-Abl, PDGFR and c-kit kinase activity[1][2].
Dovitinib-D8 (CHIR-258-D8) is the deuterium labeled Dovitinib. Dovitinib (CHIR-258) is a multi-targeted tyrosine kinase inhibitor with IC50s of 1, 2, 8/9, 10/13/8, 27/210 nM for FLT3, c-Kit, FGFR1/FGFR3, VEGFR1/VEGFR2/VEGFR3 and PDGFRα/PDGFRβ, respectively[1][2].
Sorafenib (Bay 43-9006) is a potent multikinase inhibitor with IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively.
PD180970 is a highly potent and ATP-competitive p210Bcr-Abl kinase inhibitor, with an IC50 of 5 nM for inhibiting the autophosphorylation of p210Bcr-Abl. PD180970 also inhibits Src and KIT kinase with IC50s of 0.8 nM and 50 nM, respectively. PD180970 indcues apoptosis of K562 leukemic cells, and can be used for chronic myelogenous leukemia research[1][2][3].
Multi-kinase-IN-2 (compound 7h) is an orally active and potent angiokinase inhibitor. Multi-kinase-IN-2 exhibits excellent inhibitory activity against angiokinases including VEGFR-1/2/3, PDGFRα/β, and FGFR-1, as well as LYN and c-KIT kinases. Multi-kinase-IN-2 significantly attenuates phosphorylation of AKT and ERK proteins. Multi-kinase-IN-2 induces cell apoptosis. Multi-kinase-IN-2 shows anticancer activity[1].
Pazopanib-13C,d3 is the deuterium and 13C labeled Pazopanib[1]. Pazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with IC50s of 10, 30, 47, 84, 74, 140 and 146 nM, respectively[2][3].
Motesanib is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50s of 2 nM/3 nM/6 nM, respectively, and has similar activity against Kit, and is appr 10-fold more selective for VEGFR than PDGFR and Ret.
Cabozantinib-d4 is deuterium labeled Cabozantinib. Cabozantinib is a potent multiple receptor tyrosine kinases (RTKs) inhibitor that inhibits VEGFR2, c-Met, Kit, Axl and Flt3 with IC50s of 0.035, 1.3, 4.6, 7 and 11.3 nM, respectively.
AZD2932 is a potent and multi-targeted kinase inhibitor VEGFR2, PDGFβ, Flt-3 and c-Kit with IC50s of 8, 4, 7 and 9 nM in cell assay, respectively.
Masitinib is an orally available Kit inhibitor with an IC50 of 200 nM. It also inhibits PDGFRα/β with an IC50 of 540 nM/800 nM nM.
Imatinib D8 (STI571 D8) is a deuterium labeled Imatinib (STI571). Imatinib is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, v-Abl, PDGFR and c-kit kinase activity[1][2].
Sitravatinib is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth with IC50 of 3980 nmol/Lin vitro: MGCD516 is superior to other multi-kinase inhibitors in inhibiting cell proliferation, RTK phosphorylation, and phosphorylation of downstream effectors. MGCD516 is unique in a way that it has broad spectrum activity against many RTKs including c-Met, c-Kit, Axl, PDGFR, and Eph receptors that are known to play a role in driving sarcoma cell growthIn vivo: MGCD516 induces significant tumor growth suppression than imatinib and crizotinib.
Avapritinib is a potent and selective exon 17 mutant KIT kinase inhibitor with IC50 of 0.27 nM for KIT D816V.
c-Kit-IN-5 is potent inhibitor of c-Kit, with IC50s of 22 nM and 16 nM in kinase assay and cell assay, respectively. c-Kit-IN-5 shows more than 200-fold selectivity for c-Kit over KDR, p38, Lck, and Src. c-Kit-IN-5 also exhibits desirable pharmacokinetic properties[1].
Telatinib mesylate (Bay 57-9352 mesylate) is a potent and orally active VEGFR2, VEGFR3, PDGFα, and c-Kit inhibitor with IC50s of 6 nM, 4 nM, 15 nM and 1 nM, respectively[1].
Telatinib (Bay 57-9352) is an orally active, small molecule inhibitor of VEGFR2, VEGFR3, PDGFα, and c-Kit with IC50s of 6, 4, 15 and 1 nM, respectively.
AZD3229 Tosylate is a potent pan-KIT mutant inhibitor for the treatment of gastrointestinal stromal tumors.
Pexidartinib hydrochloride (PLX-3397 hydrochloride) is a potent, selective and ATP-competitive CSF1R (cFMS) and c-Kit inhibitor, with IC50s of 20 and 10 nM, respectively. Pexidartinib exhibits 10- to 100-fold selectivity for c-Kit and CSF1R over other related kinases, such as FLT3, KDR (VEGFR2), LCK, FLT1 (VEGFR1) and NTRK3 (TRKC), with IC50s of 160, 350, 860, 880, and 890 nM, respectively[1].
Apatinib free base (YN968D1 free base) is an orally bioavailable tyrosine kinase inhibitor, which selectively targets VEGFR-2 (IC50=1 nM). Apatinib free base (YN968D1 free base) is an anti-angiogenic drug for the treatment of advanced or metastatic gastric cancer. Apatinib free base (YN968D1 free base) potently inhibits Ret, c-Kit and c-Src with IC50s of 13, 429 and 530 nM, respectively. It also inhibits cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ[1][2][3].
ISCK03 is a specific SCF/c-Kit inhibitor.
Amuvatinib (MP-470) is a potent and multi-targeted inhibitor of c-Kit, PDGFRα and Flt3 with IC50 of 10 nM, 40 nM and 81 nM, respectively.IC50 Value: 10 nM(c-KitD816H); 40 nM(PDGFRαV561D); 81 nM(Flt3D835Y) [1]Target: c-Kit; PDGFRα; FLT3in vitro: The hydrochloride salt of MP-470 also inhibits several mutants of c-Kit, including c-KitD816V, c-KitD816H, c-KitV560G, and c-KitV654A, as well as a Flt3 mutant (Flt3D835Y) and two PDGFRα mutants (PDGFRαV561D and PDGFRαD842V), with IC50 of 10 nM to 8.4 μM. MP-470 potently inhibits the proliferation of OVCAR-3, A549, NCI-H647, DMS-153, and DMS-114 cells, with IC50 of 0.9 μM–7.86 μM [1]. MP-470 also inhibits c-Kit and PDGFRα, with IC50 values of 31 μM and 27 μM, respectively. MP-470 demonstrates potent cytotoxicity against MiaPaCa-2, PANC-1, and GIST882 cells, with IC50 of 1.6 μM to 3.0 μM. MP-470 also binds to and inhibits several c-Kit mutants, including c-KitK642E, c-KitD816V, and c-KitK642E/D816V [2]. In MDA-MB-231 cells, MP-470 (1 μM) inhibits tyrosine phosphorylation of AXL [3]. In LNCaP and PC-3, but not DU145 cells, MP-470 exhibits cytotoxicity with IC50 of 4 μM and 8 μM, respectively, and induces apoptosis at 10 μM. In LNCaP cells, MP-470 (10 μM) elicits G1 arrest and decreases phosphorylation of Akt and ERK1/2 [4].in vivo: In mice xenograft models of HT-29, A549, and SB-CL2 cells, MP-470 (10 mg/kg–75 mg/kg via i.p. or 50 mg/kg–200 mg/kg via p.o.) inhibits tumor growth [1]. In mice bearing LNCaP xenograft, MP-470 (20 mg/kg) combined with Erlotinib significantly induces tumor growth inhibition (TGI) [4].
OSI-930 is a potent inhibitor of Kit, KDR and CSF-1R with IC50 of 80 nM, 9 nM and 15 nM, respectively; also potent to Flt-1, c-Raf and Lck and low activity against PDGFRα/β, Flt-3 and Abl.IC50 value: 9 nM(VEGFR2); 15 nM(CSF1R); 80 nM (Kit activated) [1]Target: VEGFR2/Kit/CSF1Rin vitro: OSI-930 inhibits the cell proliferation in the HMC-1 cell line with IC50 of 14 nM without significant effect on growth of the COLO-205 cell line that does not express a constitutively active mutant receptor tyrosine kinase. Moreover, OSI-930 also induces apoptosis in HMC-1 cell line with EC50 of 34 nM [1]. A recent study shows that OSI-930 inactivates purified, recombinant cytochrome P450 (P450) 3A4 with a Ki of 24 μM in a time- and concentration-dependent mode [2].in vivo: OSI-930, administrated at the maximally efficacious dose of 200 mg/kg by oral gavage, exhibits potent antitumor activity in a broad range of preclinical xenograft models including HMC-1, NCI-SNU-5, COLO-205 and U251 xenograft models [1].