c-Kit Inhibitor

Toceranib-d₈ is the deuterium labeled Toceranib. Toceranib (SU11654) is an orally active receptor tyrosine kinase (RTK) inhibitor, and it potently inhibits PDGFR, VEGFR, and Kit with Kis of 5 and 6 nM for PDGFRβ and Flk-1/KDR, respectively. Toceranib (SU11654) has antitumor and antiangiogenic activity, and used in the treatment of canine mast cell tumors.

APcK110 is a potent Kit inhibitor that can be used for the research of acute myeloid leukemia (AML). APcK110 induces AML cell apoptosis.

CDX-0158 (NCT02642016; KTN0158) is a humanized anti-c-Kit/CD117 IgG1κ monoclonal antibody. CDX-0158 effectively blocks the SCF-KIT signaling pathway and inhibits mast cell activation, but due to the retention of wild-type IgG1 Fc, it can induce mast cell degranulation through FcyR cross-linking, resulting in obvious infusion reactions. CDX-0158 can be used in research related to advanced refractory gastrointestinal stromal tumors.

JI6 is a potent, selective and orally active FLT3 inhibitor, with IC₅₀s of ～40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively. JI6 also inhibits JAK3 and c-Kit, with IC₅₀s of ～250 and ～500 nM, respectively. JI6 can be used for the research of acute myeloid leukemia.

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.

KI-328 is a novel inhibitor targeting KIT kinase that has selective activity against some KIT mutant kinases commonly found in acute myeloid leukemia (AML). KI-328 showed specificity for KIT kinase in in vitro kinase assays and inhibited the growth of wild-type (Wt) and mutant KIT-expressing cells, but had lower activity against D816V-KIT. Comparative analysis of the inhibitory effects of several potent KIT inhibitors on the growth of multiple mutant KIT-expressing cells showed that the multi-kinase inhibitors had comparable activity against D816V-KIT as against other mutant KITs; however, heat shock protein 90 (HSP90) inhibitors showed significant activity against D816V-KIT, inhibiting the growth of D816V-KIT-expressing cells at concentrations that did not affect the growth of other mutant KIT-expressing cells. These results suggest that potent KIT inhibitors have different activities against different types of KIT mutant kinases. Therefore, in clinical development, KIT inhibitors need to validate their activity against multiple types of KIT mutant kinases.

c-Kit-IN-11 (Compound A7) is a c-Kit inhibitor with an IC₅₀ of 76  nM for Mo7e cells. c-Kit-IN-11 can be used for inflammatory like asthma and malignant cancers research.

Anti-inflammatory agent 117 is an orally active anti-inflammatory agent and c-Kit kinase inhibitor with an IC₅₀ of 15.2 μM. Anti-inflammatory agent 117 blocks the NF-κB signaling pathway and inhibits the release of IL-6. Anti-inflammatory agent 117 exhibits anti-inflammatory effects in mouse models of acute lung injury, sepsis and ulcerative colitis. Anti-inflammatory agent 117 can be used in research related to acute lung injury, sepsis and ulcerative colitis.

c-Kit-IN-15 is a c-Kit inhibitor. c-Kit-IN-15 inhibits the c-Kit signaling pathway and suppresses cancer cell proliferation. c-Kit-IN-15 can be used in research related to hepatocellular carcinoma and breast cancer.

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.

GW694590A (UNC10112731) is a MYC protein stabilizer that increases endogenous MYC protein levels. GW694590A also targets receptor tyrosine kinases, inhibiting DDR2, KIT and PDGFRα by 81% at 1 μM. , 68% and 67%. GW694590A is a protein kinase inhibitor across ATP-dependent and -independent luciferases with potential effects on the Fluc reporter gene.

Multi-kinase-IN-6 (compound 10e) is a multikinase inhibitor that shows good enzyme inhibitory activity against TrkA, ALK2, c-KIT, EGFR, PIM1, CK2α, CHK1, and CDK2. Multi-kinase-IN-6 reveals antiproliferative activity against MCF7, HCT116 and EKVX with IC₅₀ values of 3.36 μM, 1.40 μM and 3.49 μM, respectively. Multi-kinase-IN-6 shows cell cycle arrest at the G1/S phase and G1 phase in MCF7 and HCT116 cells with good apoptotic effect.

Multi-kinase-IN-5 (compound 15c) is a promising multi-kinase inhibitory agent. Multi-kinase-IN-5 inhibits a panel of protein kinases (RET, KIT, cMet, VEGFR1,2, FGFR1, PDGFR and BRAF), showing % inhibition of 74%, 31%, 62%, 40%, 73%, 74%, 59%, and 69%, respectively, and IC₅₀ of 1.287, 0.117 and 1.185 μM against FGFR1, VEGFR, and RET kinases, respectively.

c-Kit-IN-8 (Compound 53) is an inhibitor for c-Kit kinase, that inhibits uKIT kinase with an IC₅₀ > 1 μM. c-Kit-IN-8 inhibits the proliferation of cancer cell GIST430 and BaF3 wildtype and mutants with IC₅₀ > 0.1 μM.

VEGFR2-IN-84 is an orally active, multi-targeted tyrosine kinase inhibitor based on a naphthalene ring scaffold. VEGFR2-IN-84 inhibits VEGFR2 with sub-nanomolar affinity and broadly targets kinases including Kit, FGFR, PDGFR, and Ret. By competitively binding to the ATP-binding pocket, VEGFR2-IN-84 blocks the phosphorylation of VEGFR2 and its downstream AKT/ERK signaling pathway, thereby significantly inhibiting endothelial cell proliferation, migration, and tumor angiogenesis. VEGFR2-IN-84 exhibits broad-spectrum antiproliferative activity against various solid tumors such as liver cancer, lung cancer, and renal cancer, shows weak toxicity to normal cells, and has superior potency to Lenvatinib (HY-10981). VEGFR2-IN-84 possesses favorable pharmacokinetic properties and high safety (LD₅₀>2000 mg/kg), and can be used in related studies of various malignant tumors.

c-Kit-IN-10 (Compound 1) is a c-Kit inhibitor. c-Kit-IN-10 can be used for inflammatory like asthma and malignant cancers research.

Tafetinib (SIM010603) analogue 1 is an analog of the tyrosine kinase receptor inhibitor Tafetinib (SIM010603)..

c-Kit-IN-6 (Compound 101) is an inhibitor of c-Kit with an IC₅₀ value ranging between 100 nM and 1 μM. Additionally, c-Kit-IN-6 can inhibit the proliferation of GIST430 and BaF3 mutant cells.

Kit-IN-9 (Compound D9) is an inhibitor of c-Kit. c-Kit-IN-9 inhibits the inflammatory responses in J774A.1, RAW264.7, MPMs cells and lung tissues by blocking the activation of the NF-κB pathway induced by LPS (HY-D1056). Meanwhile, c-Kit-IN-9 exhibits good anti-inflammatory activities in acute lung injury and sepsis mouse models. c-Kit-IN-9 can be used in the research of acute lung injury and related inflammatory diseases.

KIT/PDGFRA-IN-3 is a KIT and PDGFRA mutant kinase inhibitor, with an IC₅₀ of 9 nM against human PDGFRA. KIT/PDGFRA-IN-3 inhibits the kinase activity of KIT, exhibiting superior selectivity for mutant KIT over wild-type KIT. KIT/PDGFRA-IN-3 suppresses the kinase activity of PDGFRA and blocks downstream signaling pathways. KIT/PDGFRA-IN-3 can be used in studies of gastrointestinal stromal tumors.