FGFR1/DDR2 inhibitor 1

• CAT Number: I019072
• CAS Number: 2308497-58-5
• Molecular Formula: C28H22F3N5O
• Molecular Weight: 501.50
• Purity: ≥95%
• Synonyms: 3-[3-(1-cyclopropylpyrazol-4-yl)-1H-indazol-6-yl]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide
• InChI: InChI=1S/C28H22F3N5O/c1-16-5-6-18(27(37)33-21-4-2-3-20(13-21)28(29,30)31)11-24(16)17-7-10-23-25(12-17)34-35-26(23)19-14-32-36(15-19)22-8-9-22/h2-7,10-15,22H,8-9H2,1H3,(H,33,37)(H,34,35)
• InChIKey: ZEOWTGPWHLSLOG-UHFFFAOYSA-N
• SMILES: CC1=C(C=C(C=C1)C(=O)NC2=CC=CC(=C2)C(F)(F)F)C3=CC4=C(C=C3)C(=NN4)C5=CN(N=C5)C6CC6

FGFR1/DDR2 inhibitor 1 is an orally active inhibitor of fibroblast growth factor receptor 1 (FGFR1) and discoindin domain receptor 2 (DDR2), with IC50 values of 31.1 nM and 3.2 nM, respectively. Antitumor activity[1].
FGFR1/DDR2 inhibitor 1 (compound 11k) (25-200 μM; 2 hours) shows significant inhibition of FGFR2 phosphorylation in a dose-dependent manner in SNU16 cells. FGFR1/DDR2 inhibitor 1 shows (60-250 μM; 2 hours) significant inhibition of DDR2 phosphorylation in a dose-dependent manner in H2286 cells[1].
FGFR1/DDR2 inhibitor 1 significantly inhibits the proliferation of FGFR-driven cancer cell lines with IC50s of 108.4, 93.4, 31.8 and 306.6 nM against KG-1, SNU-16, NCI-H716 and UMUC14 respectively. FGFR1/DDR2 inhibitor 1 demonstrates substantially activity against the DDR2-driven cancer cell line NCI-H2286 (93.0 nM)[1].
FGFR1/DDR2 inhibitor 1 (10-20 mg/kg; p.o.; once daily for 7 days) has profound anti-tumor efficacy in NCI-H1581 tumor model[1].
SCID mice bearing NCI-H2286 tumors were randomized and treated with FGFR1/DDR2 inhibitor 1 at doses of 10 mg/kg for 10 consecutive days. FGFR1/DDR2 inhibitor 1 could suppress tumor growth with tumor growth inhibition rates (TGI) of 82.8%[1].

Reference

[1]. Wang Q, et al. Discovery and optimization of a series of 3-substituted indazole derivatives as multi-target kinase inhibitors for the treatment of lung squamous cell carcinoma. Eur J Med Chem. 2019 Feb 1;163:671-689.
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