ASP5878

ASP5878 is an inhibitor of wild-type FGFR1, -2, -3, and -4 (IC50s = 0.47, 0.6, 0.74, and 3.5 nM, respectively) and mutant FGFR3K650E, FGFR3K560M, and FGFR4N535K (IC50s = 1.6, 4.2, and 78 nM, respectively). It is selective for these FGFRs over a panel of 128 additional kinases at 200 nM but does inhibit VEGFR2 and CSF-1 receptor tyrosine kinase (FMS, IC50s = 25 and 150 nM, respectively). It selectively inhibits the proliferation of urothelial cancer cell lines with FGFR gene alterations (IC50s = FGFR gene alterations (IC50s = >300 nM). ASP5878 also inhibits the proliferation of adriamycin-resistant UM-UC-14 bladder cancer cells and gemcitabine-resistant RT-112 bladder cancer cells (IC50s = 11 and 10 nM, respectively). In vivo, ASP5878 (3 mg/kg) induces tumor regression in a UM-UC-14 mouse xenograft model. It also increases femur and tibia length and femur growth plate cartilage thickness in Fgfr3G380R male mice in a model of achondroplasia when administered at a dose of 300 µg/kg.Formal Name: 4-[[5-[(2,6-difluoro-3,5-dimethoxyphenyl)methoxy]-2-pyrimidinyl]amino]-1H-pyrazole-1-ethanol. CAS Number: 1453208-66-6. Molecular Formula: C18H19F2N5O4. Formula Weight: 407.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Slightly soluble: 0.1-1 mg/ml, DMSO: Sparingly soluble: 1-10 mg/ml. SMILES: FC(C(OC)=CC(OC)=C1F)=C1COC2=CN=C(N=C2)NC3=CN(CCO)N=C3. InChi Code: InChI=1S/C18H19F2N5O4/c1-27-14-5-15(28-2)17(20)13(16(14)19)10-29-12-7-21-18(22-8-12)24-11-6-23-25(9-11)3-4-26/h5-9,26H,3-4,10H2,1-2H3,(H,21,22,24). InChi Key: VDZZYOJYLLNBTD-UHFFFAOYSA-N.