PDGFR Inhibitor

PP487 is a selective dual inhibitor of Tyrosine kinase/PI3-K, with IC₅₀ values of 0.017 μM, 0.072 μM, 0.004 μM, 0.01 μM, 0.55 μM, 0.22 μM, and < 0.01 μM against DNA-PK, mTOR, Hck, Src, EGFR, EphB4, and PDGFR, respectively. PP487 can be used in cancer research.

Tyrosine kinase-IN-11 (Compound 4b) is a tyrosine kinase inhibitor. Tyrosine kinase-IN-11 decreases general tyrosine kinase activity, selectively inhibits PDGFR-β, SRC, and c-MET kinases. Tyrosine kinase-IN-11 induces apoptosis, accompanied by reduced ERK signalings. Tyrosine kinase-IN-11 exhibits selective anticancer activity against pancreatic cancer and renal cancer.

BLU-654 is an orally active antineoplastic agent and KIT inhibitor. BLU-654 is a highly selective inhibitor targeting wild-type KIT, PDGFRβ, and KIT^V654A over most other kinases in the kinome. BLU-654 exerts sustained antineoplastic activity in KIT^V654A cell-derived xenograft mouse models. BLU-654 can be used in research related to Imatinib (HY-15463)-resistant gastrointestinal stromal tumors.

GSK190937 is a type II platelet-derived growth factor receptor alpha (PDGFRA) human kinase inhibitor with antimalarial activity. GSK190937 can inhibit the formation of hemozoin in the malaria parasite, resulting in the accumulation of free hemoglobin within the malaria parasite. GSK190937 shows IC₅₀ values of 0.22, 0.59 and 0.25 μM against P. falciparum NF54, K1 and Dd2 parasite. GSK190937 shows an IC₅₀ of 25 μM for CHO cells. GSK190937 can be used for research of malaria.

UNC9750 is an inositol phosphate multikinase (IPMK) inhibitor with IC₅₀ values ​​of 31.6 and 374 nM for IPMK and IP6K2, respectively.. UNC9750 inhibits cellular accumulation of InsP₅, the direct product of IPMK kinase activity, while having no effect on either InsP6 or InsP₇ levels. UNC9750 has ≥ 75% inhibition of four kinases (DAPK1, DYRK1B, PDGFR, and KDR). UNC9750 can be used for the study of glioblastoma.

JI-101 hydrochloride is an orally active angiogenesis inhibitor and anticancer agent with 55% oral bioavailability in Sprague Dawley rats, high permeability, and no P-gp substrate activity.JI-101 hydrochloride modulates angiogenesis signaling pathways in tumor vessel beds, downregulates EphB4, targets EphB4, VEGFR-2, and PDGFR-β, and inhibits multiple stages of tumor angiogenesis.JI-101 hydrochloride exerts activity against cancer cells and xenografts, exhibits mild to moderate inhibition of CYP3A4, and shows stability in pre-clinical and human liver microsomes.JI-101 hydrochloride undergoes rapid oral absorption in Sprague Dawley rats, has extensive tissue distribution with preferred lung uptake, and is excreted via bile with mono- and di-hydroxy metabolites, with feces as the primary elimination route.JI-101 hydrochloride can be used for the research of ovarian cancer and solid tumors.

KBP-7018 hydrochloride is an orally active, tyrosine kinase-selective multi-kinase inhibitor with an IC₅₀ value of 10 nM against c-KIT, 7.6 nM against RET, and 25 nM against human PDGFR. KBP-7018 hydrochloride improves survival rates in a mouse model of pulmonary fibrosis. KBP-7018 hydrochloride can be used in research related to idiopathic pulmonary fibrosis.

VEGFR-2-IN-88 is a VEGFR-2 inhibitor with an IC₅₀ of 0.202 μM. VEGFR-2-IN-88 potently inhibits EGFR (IC₅₀ = 0.139 μM), and moderately inhibits PDGFR-β (IC₅₀ of 0.236 μM) and c-Met (IC₅₀ of 0.281 μM). VEGFR-2-IN-88 acts as a cell cycle inhibitor that arrests cells at the G₀/G₁ phase. VEGFR-2-IN-88 induces Apoptosis. VEGFR-2-IN-88 downregulates serum AST and ALT levels. VEGFR-2-IN-88 exerts selective anticancer effects. VEGFR-2-IN-88 reduces liver weight in in vivo models. VEGFR-2-IN-88 can be used in research related to hepatocellular carcinoma.

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.

CDK2/FLT4/PDGFRA-IN-1 (Compound 4a) is a potent inhibitor of CDK2/cyclin A, FLT4 (VEGFR3) and PDGFRA, with IC₅₀s of 1.672, 0.554, and 0.629 μM, respectively. CDK2/FLT4/PDGFRA-IN-1 exhibits potent antiproliferative effects against cancer cells (lung EBC-1, pancreatic ductal adenocarcinoma AsPC-1, colorectal HT-29 cells). CDK2/FLT4/PDGFRA-IN-1 can also induce apoptosis in cancer cells.

PDGFRA/CAIX/XII-IN-1 is an inhibitor of PDGFRA, CA IX and CA XII, with an IC₅₀ of 20 nM against PDGFRA, a K_i of 93.3 nM against CA IX, and a K_i of 80.0 nM against CA XII. PDGFRA/CAIX/XII-IN-1 binds to the ATP-binding pocket of PDGFRA and blocks the downstream STAT3, AKT and ERK1/2 signaling pathways. PDGFRA/CAIX/XII-IN-1 induces G0/G1 cell cycle arrest and endogenous apoptosis (Apoptosis), including cleavage of PARP-1, caspase-9 and caspase-3, activation of caspase 3/7, and down-regulation of Mcl-1. PDGFRA/CAIX/XII-IN-1 exhibits antiproliferative activity in eosinophilic leukemia cells. PDGFRA/CAIX/XII-IN-1 can be used for the research of leukemia.

YTB53 is a MNK1 and MNK2 inhibitor with IC₅₀s of 37 nM and 9 nM, respectively. YTB53 inhibits PDGFRα, TRKB and FLT3 in leukemia cells. YTB53 induces cell cycle arrest, apoptosis, pyroptosis, and mitochondrial dysfunction. YTB53 exhibits antiangiogenic effects. YTB53 can be used for the study of acute myeloid leukemia (AML).

RET-IN-33 is a moderately selective inhibitor of RET mutants. RET-IN-33 potently inhibits G810 mutants, with IC₅₀ values of 4.43 nM (G810R), 3.28 nM (G810C) and 0.51 nM (G810S), respectively. RET-IN-33 also inhibits other RET mutants: V804M (IC₅₀ 0.73 nM), V804L (IC₅₀ 0.36 nM), Y806H (IC₅₀ 0.74 nM) and M918T (IC₅₀ 0.55 nM). RET-IN-33 also inhibits other kinases, with an IC₅₀ of 1.50 nM against VEGFR2 and 1.60 nM against PDGFRα. RET-IN-33 blocks the autophosphorylation of RET mutants and the downstream SHC/AKT/ERK signaling pathway. RET-IN-33 selectively inhibits the proliferation of RET-driven cell models without affecting non-RET-dependent or normal cells. RET-IN-33 exhibits dose-dependent antitumor efficacy in RET-driven xenograft models. RET-IN-33 can be used for the research of medullary thyroid carcinoma, papillary thyroid carcinoma and non-small cell lung cancer.

LY2457546 is a potent and orally active multi-targeted anti-angiogenic tyrosine kinases inhibitor. LY2457546 demonstrates potent activity against targets that include VEGFR2, PDGFRβ, FLT-3, Tie-2 and members of the Eph family of receptors. LY2457546 can be used for the research of cancer, such as 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.

FGFR1/VEGFR2-IN-2 (compound 6l) is a VEGFR2/FGFR1 dual inhibitor. The IC₅₀ values for VEGFR2 and FGFR1 are 0.025 µM and 0.026 µM respectively, and for EGFR and PDGFR-β, the IC₅₀ values are 0.106 µM and 0.077 µM. FGFR1/VEGFR2-IN-2 showes significant anti-cancer activity (GI=60.38%) on NCI-60 cell line, with an IC₅₀ of 8.51 µM in T-47D cell line and anti-migration. FGFR1/VEGFR2-IN-2 acts to arrest cells in the G1 phase and promote apoptosis and necrosis; the IC₅₀ for MCF-7 cell line exceeds 100 µM, and the IC₅₀ for MDA-MB-231 is 69.17 µM, non-toxic to normal cells.

Multi-kinase-IN-3 (compound 2) is a potent angiokinase inhibitor. Multi-kinase-IN-3 shows inhibition activity against VEGFR-2 and PDGFRβ, with IC₅₀ values of 58.3 and 55 nM, respectively.

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.

1-Phenyl-1H-benzimidazole-6-carboxylic acid is a PDGF inhibitor.

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.