fgfr4-in-1

FGFR4-IN-1 is a potent FGFR4 inhibitor (IC50: 0.7 nM).

FGFR4-IN-14 (Compound 27i) is a selective FGFR4 inhibitor with an IC50 of 2.4 nM, effectively inhibiting cell proliferation in V550L and N535K mutant strains. It shows IC50 values of 21 nM against Huh7 cells, 2.5 nM against BaF3 ETV6-FGFR4-V550L cells, and 171 nM against BaF3 ETV6-FGFR4-N535K cells. FGFR4-IN-14 demonstrates significant antitumor efficacy in the Huh7 xenograft model and is utilized in hepatocellular carcinoma (HCC) research [1].

FGFR4-IN-16 (CY-15-2) is a covalent inhibitor of FGFR-4, employed in cancer research [1].

FGFR4-IN-17 (Compound (S)-23), a piperazinyl diflurindan derivative featuring a pyridinyl group, functions as an inhibitor of FGFR. It exhibits IC 50 values of 24.2 nM for FGFR1, 16.1 nM for FGFR2, 78.0 nM for FGFR3, and 68.0 nM for FGFR4. Notably, FGFR4-IN-17 demonstrates significant antitumor activity [1].

FGFR4-IN-10 (compound 5a) is a selective and potent FGFR4 inhibitor (IC50: 70.7 nM) and does not inhibit other FGFR family members (i.e., FGFR1, FGFR2, and FGFR3).

FGFR4-IN-11 is a selective, potent, covalently bound FGFR4 inhibitor (IC50: 2.1 nM). FGFR4-IN-11 significantly inhibits the FGF19 FGFR4 signaling pathway and exhibits anticancer effects.

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.

BW710 is an orally active inhibitor specifically targeting fibroblast growth factor receptor 2 (FGFR2). It effectively inhibits the proliferation of BaF3-FGFR2 cells with an IC50 value of 2.8 nM. BW710 completely suppresses FGFR2 enzymatic activity and demonstrates selectivity among 75 tyrosine kinases, including FGFR1, FGFR3, and FGFR4, at a 1 μM concentration. Additionally, BW710 impedes FGFR2 signaling and selectively inhibits the proliferation of cancer cells driven by FGFR2. It exhibits promising pharmacokinetic properties, with an oral bioavailability of 29% in mice.

FGFR4-IN-5, a covalent FGFR4 inhibitor, demonstrates potency and selectivity with an IC50 value of 6.5 nM. Exhibiting significant in vivo anti-tumor activity, it is applicable for research in hepatocellular carcinoma [1].

FGFR-IN-2 (compound 1) is a potent FGFR inhibitor, targeting FGFR1 (IC50: 7.3 nM), FGFR2 (IC50: 4.3 nM), FGFR3 (IC50: 7.6 nM), and FGFR4 (IC50: 11 nM).

FGFR4-IN-8 (Compound 7v) is an ATP-competitive inhibitor that covalently and selectively targets both wild-type and gatekeeper mutant forms of FGFR4. It exhibits inhibitory potency with IC50 values of 0.5 nM for FGFR4, 0.25 nM for FGFR4 V550L, 1.6 nM for FGFR4 V550M, and 931 nM for FGFR4 C552S. Additionally, FGFR4-IN-8 shows potent antiproliferative effects on Hep3B hepatocellular carcinoma cells (IC50 of 29 nM) and demonstrates moderate antitumor efficacy in vivo in a Huh-7 xenograft model in nude mice [1].

FGFR-IN-11 (compound I-5) is an orally active, covalent inhibitor of FGFR, with IC50 values of 9.9 nM (FGFR1), 3.1 nM (FGFR2), 16 nM (FGFR3), and 1.8 nM (FGFR4). This compound demonstrates nanomolar potency in inhibiting the proliferation of various cancer cells and significantly hinders tumor growth in xenograft mouse models [1].

S6K2-IN-1 (Compound 2) is an S6K2 inhibitor with an IC50 of 22 nM and displays inhibitory activity against FGFR4 with an IC50 of 216 nM, demonstrating acceptable stability in mouse liver microsomes [1].

CYY292 is a chemical compound acting as an inhibitor of PDGFRα, PDGFRβ, FGFR1, -2, and -3, with respective IC50 values of 5.35, 4.6, 28, 28, and 78 nM. It exhibits selectivity over FGFR4 (IC50 > 1,000 nM) while also targeting c-Kit, VEGFR2, VEGFR1, and IGF-1R (IC50 values of 67, 33, 36, and 75 nM, respectively). Additionally, CYY292 inhibits EGFR, BTK, Cdk4/cyclin D3, and MET with IC50 values of 128, 198, 214, and 396 nM, respectively. This compound demonstrates efficacy in arresting the proliferation of various osteosarcoma cell lines—MG-63, U2OS, MNNG/HOS, and Saos-2—with IC50s ranging from 0.72 to 1.36 µM. Moreover, CYY292 at 0.3 and 0.5 µM concentrations inhibits migration and invasion in glioblastoma cells (U87MG and LN-229) and, at a dose of 30 mg/kg, decreases tumor volume and enhances survival in a U87MG orthotopic mouse xenograft model.

CXF-009 is a selective covalent inhibitor of FGFR4, with an IC₅₀ of 48 nM, targeting Cys477 and Cys552. It can be utilized in the study of hepatocellular carcinoma [1].

FGFR-IN-13 (compound III-30), an irreversible covalent inhibitor of the fibroblast growth factor receptor (FGFR), effectively modulates signaling through FGFR1 (IC 50 = 0.20 ± 0.02 nM) and FGFR4 (IC 50 = 0.40 ± 0.03 nM). It suppresses the expression of crucial proteins such as total-PARP and Bcl-2, while enhancing the expression of Cleaved-PARP and Bax in a dose-dependent manner. Notably, FGFR-IN-13 demonstrates considerable antitumor and oral activity [1].