FGFR Inhibitor

FGFR1 inhibitor-8 (Compound 9) is a FGFR1 inhibitor (IC₅₀s: 0.5 nM). FGFR1 inhibitor-8 binds to the ATP-binding pocket of FGFR1. FGFR1 inhibitor-8 has 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.

FGFR4-IN-9 (Compound 6O) is a selective FGFR4 inhibitor with an IC₅₀ of 75.3 nM. FGFR4-IN-9 effectively inhibits both the growth and angiogenesis of HCC.

FGFR-IN-12 (example 14), a pyrimidinyl aryl urea derivative, is a potent FGFR inhibitor.

FGFR-IN-17 (Compound 12l) is an orally active irreversible inhibitor of FGFR, which has a strong inhibitory effect on FGFR and its mutants. FGFR-IN-17 can inhibit the proliferation and migration, and induce apoptosis of non-small cell lung cancer cells. FGFR-IN-17 has anti-tumor activity.

FGFR4-IN-7 (Compound C3) is a covalent reversible FGFR4 inhibitor with an IC₅₀ value of 0.42 μM. FGFR4-IN-7 induces apoptosis via the FGFR4 signaling pathway blockage. FGFR4-IN-7 can be used for the research of hepatocellular carcinoma (HCC).

FGFR3-IN-11(compound B11) is a Fibroblast growth factor receptor 3 (FGFR3) inhibitor with a K_a value of 4.8 μM. FGFR3-IN-11 induces apoptosis, suppresses colony formation, and causes dose-dependent G0/G1 cell cycle arrest in cancer cells. FGFR3-IN-11 exerts anticancer activity against cancer cells with minimal toxicity toward normal hepatocytes and demonstrates tumor growth suppression in xenograft mouse models. FGFR3-IN-11 can be used for the research of hepatocellular carcinoma.

LHQ766 is a highly selective, orally active, covalent FGFR2 inhibitor with an IC₅₀ of 7.3 nM. LHQ766 significantly suppresses phosphorylation of FGFR2 and its downstream signaling molecules FRS2-a, Akt and ERK1/2. LHQ766 selectively suppresses the proliferation of FGFR2-driven cancer cells.

FGFR2-IN-4 is a selective, orally active FGFR2 inhibitor, with IC₅₀ values of 10.0 nM and 5.8 nM against wild-type FGFR2 and the FGFR2^V565F mutant, respectively. FGFR2-IN-4 induces necroptosis in FGFR2-driven tumor cells. FGFR2-IN-4 induces tumor regression in xenograft models harboring FGFR2 inhibitor-resistant mutations without altering serum phosphate levels. FGFR2-IN-4 is used to investigate FGFR2-driven malignancies, including intrahepatic cholangiocarcinoma and gastric cancer.

10-Deacetyltaxol (Standard) is the analytical standard of 10-Deacetyltaxol. This product is intended for research and analytical applications. 10-Deacetyltaxol (10-Deacetylpaclitaxel) is a taxane derivative isolated from Taxus wallichiana Zucc. 10-Deacetyltaxol (10-Deacetylpaclitaxel) promotes the polymerization of tubulin and to inhibit the depolymerization of microtubules induced by cold or by calcium ions in vitro. 10-Deacetyltaxol (10-Deacetylpaclitaxel) exhibits cytotoxicity in human glial and neuroblastoma cell-lines.

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.

HDAC-IN-50 is a potent and orally active FGFR and HDAC dual inhibitor with IC₅₀ values of 0.18, 1.2, 0.46, 1.4, 1.3, 1.6, 2.6, 13 nM for FGFR1, FGFR2, FGFR3, FGFR4, HDAC1, HDAC2, HDAC6, HDAC8, respectively. HDAC-IN-50 induces Apoptosis and cell cycle arrest at G0/G1 phase. HDAC-IN-50 decreases the expression of pFGFR1, pERK, pSTAT3. HDAC-IN-50 shows anti-tumor activity.

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.

FGFR1 inhibitor-6 is a potent FGFR1 inhibitor with an IC₅₀ value of 16.31 nM. FGFR1 inhibitor-6 shows cytotoxic activities. FGFR1 inhibitor-6 induces apoptosis and cell cycle arrest at pre-G1 and G2/M phase.

Arg-IN-1 is a selective Arginine (Arg)-targeting covalent inhibitor with IC₅₀s of 9.7 nM and 30.4 nM for FGFR2 and FGFR3,respectively. Arg-IN-1 has the potential to avoid FGFR1/4-targeted toxicity as well as conquer acquired on-target resistance, potential for FGFR-targeting cancer therapy.

CEP-11981 (tosylate) (ESK981 (tosylate), BOL 303213X (tosylate)) is an orally active tyrosine kinase inhibitor (TKI), which can target TIE2, VEGFR1-3 and FGFR1, and has potential anti-tumor and anti-angiogenic effects.

BW710 is an orally active fibroblast growth factor receptor 2 (FGFR2) inhibitor. BW710 inhibits the proliferation of BaF3-FGFR2 cells with an IC₅₀ of 2.8 nM. BW710 abolishes FGFR2 enzymatic activity and is selective against other 75 tyrosine kinases including FGFR1, FGFR3, and FGFR4 at 1 μM. BW710 suppresses the FGFR2 signaling and selectively inhibits FGFR2-driven cancer cell proliferation. BW710 displays reasonable pharmacokinetic properties with an oral bioavailability of 29 % in mice.

VSPPLTLGQLLS TFA is a small peptide FGFR3 inhibitor, peptide P3, inhibits FGFR3 phosphorylation. VSPPLTLGQLLS TFA inhibits 9-cisRA-induced tracheal lymphangiogenesis and blocks lymphatic endothelial cell (LEC) proliferation, migration, and tubule formation.

FGFR-IN-25 (Compound 19E) is a FGFR inhibitor (IC₅₀s: 1.30 nM and 0.85 nM for FGFR1 and FGFR2, respectively) and radiosensitizer. FGFR-IN-25 effectively reduces the phosphorylation of FGFR1 and its key downstream effectors, pAKT and pERK. FGFR-IN-25 exerts broad-spectrum antitumor activity against gastric cancer, colorectal carcinoma, hepatocellular carcinoma, breast cancer, triple-negative breast cancer, and glioblastoma. FGFR-IN-25, when combined with radiotherapy, synergistically activates the ROS-Caspase-3-GSDME axis, downregulates PD-L1 expression, and induces immunogenic cell death (ICD). FGFR-IN-25 combined with radiotherapy improves the antitumor efficacy.

Glu-IN-1 (compound AF1) is a covalent and selective FGFR2 inhibitor with an IC₅₀ of 1.6 μM. Glu-IN-1 covalently modifies Glu489 in FGFR2.