Derazantinib

Derazantinib is a multi-kinase inhibitor. It is a pan inhibitor of FGF receptors (FGFRs, IC50s = 4.5, 1.8, 4.5, and 34 nM for FGFR1, -2, -3, and -4, respectively) and also inhibits 10 receptor tyrosine kinases, 8 non-receptor tyrosine kinases, and the calcium/calmodulin-dependent protein kinase QIK in a panel of 297 kinases (IC50s = 3-31 and 9.7 nM, respectively). Derazantinib decreases phosphorylation of FGFR in COS-1 cells expressing FGFR1, -2, -3, or -4 (IC50s = 10 µM, respectively) and inhibits the growth of 15 cancer cell lines with mutant, amplified, or translocated FGFR (GI50s = 0.1-1.7 µM). It reduces tumor growth and decreases tumor protein levels of phosphorylated FGFR, FGFR substrate 2 (FRS2), and ERK in a SNU-16 mouse xenograft model when administered at doses of 50 and 75 mg/kg.Formal Name: (6R)-6-(2-fluorophenyl)-5,6-dihydro-N-[3-[2-[(2-methoxyethyl)amino]ethyl]phenyl]-benzo[h]quinazolin-2-amine. CAS Number: 1234356-69-4. Synonyms: ARQ 087. Molecular Formula: C29H29FN4O. Formula Weight: 468.6. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMF:PBS (pH 7.2) (1:3): 0.25 mg/ml, DMSO: 25 m/gml. lambdamax: 248, 281, 353 nm. SMILES: COCCNCCC1=CC=CC(NC2=NC=C3C(C4=CC=CC=C4[C@H](C5=C(F)C=CC=C5)C3)=N2)=C1. InChi Code: InChI=1S/C29H29FN4O/c1-35-16-15-31-14-13-20-7-6-8-22(17-20)33-29-32-19-21-18-26(24-10-4-5-12-27(24)30)23-9-2-3-11-25(23)28(21)34-29/h2-12,17,19,26,31H,13-16,18H2,1H3,(H,32,33,34)/t26-/m1/s1. InChi Key: KPJDVVCDVBFRMU-AREMUKBSSA-N.