fgfr2-in-3

FGFR2-IN-3 is an orally active selective FGFR2 inhibitor[1].

FGFR2-IN-3 hydrochloride is a selective, orally active FGFR2 inhibitor.

TYRA-200 is an orally active FGFR1/2/3 inhibitor that induces dose-dependent tumor regression in wild-type and mutant FGFR2 models, making it a candidate for advanced or metastatic intrahepatic cholangiocarcinoma.

FGFRs-IN-1 (Compound A16) is an orally active inhibitor targeting FGFR1/2/3/4, with IC50 values of 2.3, 7, 11, and 163 nM respectively. It also inhibits VEGFR1/2/3, Abl, and Flt3, with IC50 values of 61, 176, 112, 26, and 353 nM. The compound shows weak inhibition of CYP enzymes. FGFRs-IN-1 reduces the expression of α-SMA and collagen I, and it inhibits epithelial-mesenchymal transition (EMT) in A549 cells stimulated by TGF-β1. Additionally, FGFRs-IN-1 demonstrates anti-inflammatory activity in mouse models of lung fibrosis induced by Bleomycin and liver fibrosis induced by CCl4.

FGFR2/3-IN-2 (compound 10) is an orally active inhibitor targeting FGFR2 and FGFR3. It exhibits IC50 values of 3.7 nM for FGFR2 and 31.2 nM for FGFR3, with a pre-incubation time of 1 hour. FGFR2/3-IN-2 demonstrates selectivity over FGFR1/4 and other kinases, and does not cause diarrhea or increased serum phosphate in vivo. In the SNU-16 gastric cancer model, FGFR2/3-IN-2 can induce tumor stasis or regression.

FGFR2/3-IN-3 is a dual-target FGFR2/3 inhibitor with IC50 values of 2.7 nM (TEL-FGFR2) and 3.9 nM (TEL-FGFR3), displaying efficacy against both wild-type and mutant FGFR3. It exhibits low CYP3A4 inhibition and minimal hERG toxicity. By inhibiting mutant FGFR3-mediated pathways, FGFR2/3-IN-3 improves chondrocyte proliferation and differentiation imbalances, promoting bone growth. In a dwarfism mouse model, it demonstrates growth-promoting effects, indicating potential for treating bone development disorders such as achondroplasia (ACH).

INCB126503 is an orally active and selective inhibitor of FGFR2/3, with IC50 values of 70 nM for FGFR1, 2.1 nM for FGFR2, 1.2 nM for FGFR3, 0.92 nM for FGFR3-V555L, 0.85 nM for FGFR3-V555M, and 64 nM for FGFR4. This compound inhibits FGFR signaling in vivo without causing hyperphosphatemia and demonstrates antitumor efficacy in xenograft models with FGFR3 genetic alterations.

ISM7594 is an orally active FGFR2/3 inhibitor demonstrating broad-spectrum antiproliferative capabilities in cancer cell lines with FGFR2 or FGFR3 alterations, such as amplification, fusion, and mutation (e.g., BaF3-TEL-FGFR2-V564F with an IC50 of 0.067 nM, BaF3-TEL-FGFR2-V564I with an IC50 of 2 nM). It inhibits tumor growth in a dose-dependent manner and is suitable for research on advanced solid tumors with FGFR2/3 abnormalities.

FGFR-IN-25 (Compound 19E) is an FGFR inhibitor with IC50 values of 1.30 nM for FGFR1 and 0.85 nM for FGFR2, and also acts as a radiosensitizer. It effectively reduces the phosphorylation levels of FGFR1 and its downstream effectors, pAKT and pERK. FGFR-IN-25 exhibits broad-spectrum antitumor activity against gastric, colorectal, liver, breast, triple-negative breast cancers, and glioblastoma. When combined with radiation therapy, FGFR-IN-25 synergistically activates the ROS-Caspase-3-GSDME pathway, downregulates PD-L1 expression, and induces immunogenic cell death, thereby enhancing the antitumor effects.

FGFR-IN-24 (Compound 8r) is an inhibitor of FGFR with potent activity against FGFR1/2/3, exhibiting IC50 values of 10.0, 6.9, and 30.2 nM, respectively. It also demonstrates strong inhibitory effects on mutant forms FGFR1V561M, FGFR2V564F, and FGFR2N549K, with IC50 values of 6.8, 0.7, and 0.8 nM. FGFR-IN-24 induces apoptosis (Apoptosis) and effectively inhibits the phosphorylation of FGFR2 and its downstream signaling mediators (AKT and MAPK). It shows promising anti-tumor efficacy in the RT112/84 bladder cancer xenograft model.

LY2784544(Gandotinib (LY2784544)) is a potent JAK2 inhibitor (IC50: 3 nM), effective in JAK2V617F(Ki: 0.245 nM). The selectivity is higher 8- and 20-fold than JAK1 and JAK3.

S49076 HCl (S-49076 Hydrochloride) is an effective inhibitor of MET, AXL/MER, and FGFR1/2/3. S49076 HCl potently blocked cellular phosphorylation of MET, AXL, and FGFRs and inhibited downstream signaling in vitro and in vivo. In cell models, S49076 HCl inhibited the proliferation of MET- and FGFR2-dependent gastric cancer cells blocked MET-driven migration of lung carcinoma cells, and inhibited colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL. In tumor xenograft models, a good pharmacokinetic/pharmacodynamic relationship for MET and FGFR2 inhibition following oral administration of S49076 HCl was established and correlated well with impact on tumor growth.

FGFR3-IN-5 is a potent, selective FGFR3 inhibitor, exhibiting IC50 values of 3 nM (FGFR3), 44 nM (FGFR2), and 289 nM (FGFR1), respectively. This compound is utilized in cancer research.