PRN-1371

PRN-1371 is an irreversible covalent pan-FGFR inhibitor (IC50s = 0.7, 1.3, 4.4, and 19.3 nM for FGFR-1, -2, -3, and -4, respectively). It is selective for FGFR over VEGFR2 (IC50 = 705 nM) and a panel of 250 kinases (IC50s = >1 µM for all) but does inhibit colony stimulating factor 1 receptor (CSF1R) activity by greater than 90% at 1 µM. PRN-1371 inhibits proliferation in a panel of ten cancer cell lines containing various FGFR mutants (IC50s = 2-231 nM) and induces apoptosis in SNU-16 gastric and RT4 bladder cancer cells (EC50s = 15.9 and 11.8 nM, respectively). It reduces tumor growth in an SNU-16 mouse xenograft model and a patient-derived xenograft (PDX) mouse model of liver cancer when administered at a dose of 15 mg/kg twice per day.Formal Name: 6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)-8-[3-[4-(1-oxo-2-propen-1-yl)-1-piperazinyl]propyl]-pyrido[2,3-d]pyrimidin-7(8H)-one. CAS Number: 1802929-43-6. Molecular Formula: C26H30Cl2N6O4. Formula Weight: 561.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: 15 mg/ml. lambdamax: 343 nm. SMILES: O=C(N1CCN(CCCN2C(C(C3=C(C(OC)=CC(OC)=C3Cl)Cl)=CC4=C2N=C(NC)N=C4)=O)CC1)C=C. InChi Code: InChI=1S/C26H30Cl2N6O4/c1-5-20(35)33-11-9-32(10-12-33)7-6-8-34-24-16(15-30-26(29-2)31-24)13-17(25(34)36)21-22(27)18(37-3)14-19(38-4)23(21)28/h5,13-15H,1,6-12H2,2-4H3,(H,29,30,31). InChi Key: PUIXMSRTTHLNKI-UHFFFAOYSA-N.