CPL304110

• CAT Number: I045438
• CAS Number: 1627826-19-0
• Molecular Formula: C25H30N6O2
• Molecular Weight: 446.54
• Purity: ≥95%
• Synonyms: 2-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
• InChI: InChI=1S/C25H30N6O2/c1-30-8-10-31(11-9-30)19-6-7-22-23(15-19)27-25(26-22)24-14-18(28-29-24)5-4-17-12-20(32-2)16-21(13-17)33-3/h6-7,12-16H,4-5,8-11H2,1-3H3,(H,26,27)(H,28,29)
• InChIKey: QHCGPJPIPKDWAT-UHFFFAOYSA-N
• SMILES: CN1CCN(CC1)C2=CC3=C(C=C2)N=C(N3)C4=NNC(=C4)CCC5=CC(=CC(=C5)OC)OC

CPL304110 is a potent, orally active and selective inhibitor of fibroblast growth factor receptors FGFR (1-3), with IC50 values of 0.75 nM, 0.5 nM, and 3.05 nM for FGFR (1-3), respectively[1].
CPL304110 (0-0.6 μM) dose-dependently inhibits FGFR2 phosphorylation and downstream signaling (p-ERK)[1].
CPL304110 (compound 56q) exhibits in SNU-16 proliferation assay with an IC50 of 85.64 nM[1].
CPL304110 (compound 56q) demonstrats a more than 45-fold, 345-fold, 395-fold and 680-fold selectivity over KDR (VEGFR2), Flt3, Aura A and PDGFRb, respectively relative to FGFR2, and no significant inhibitory effects were observed with other tyrosine kinases[1].
CPL304110 (p.o., 40 mg/kg) exhibits a t1/2 of 2 h and Cmax of 3369 ng/mL in mice[1].
CPL304110 (compound 56q, 2 X 20 mg/kg) significantly inhibits tumor growth in mice without significant body loss or any toxicity. On day 21 (D21, day of termination) the tumor growth inhibition (TGI) is 64% for dosing 20 mg/kg twice a day[1].

Reference

[1]. Abdellah Yamani, et al. Discovery and optimization of novel pyrazole-benzimidazole CPL304110, as a potent and selective inhibitor of fibroblast growth factor receptors FGFR (1-3). Eur J Med Chem. 2020 Nov 7;112990.
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