PRN1371 是高度选择性和有效的 FGFR1-4 和 CSF1R 抑制剂，对FGFR1，FGFR2，FGFR3，FGFR4 和 CSF1R 的 IC₅₀ 值分别为 0.6，1.3，4.1，19.3 和 8.1 nM。

PRN1371 is a highly selective and potent FGFR1-4 and CSF1R inhibitor with IC 50 s of 0.6, 1.3, 4.1, 19.3 and 8.1 nM for FGFR1, FGFR2, FGFR3, FGFR4 and CSF1R, respectively.

Solid

FGFR1 0.6 nM (IC50) FGFR2 1.3 nM (IC5

PRN1371 presents a unique profile of high biochemical and cellular potency (FGFR1 IC50=0.6 nM, SNU16 IC50=2.6 nM), prolonged target engagement (FGFR1 occupancy 24 h=96%), < 30% hERG inhibition at 1 μM, and good predicted ADME stability with BME reactivity Kd>100 μM. Broader kinome-wide biochemical profiling of PRN1371 against 251 kinases identifies only FGFR1?4 and CSF1R as being potently inhibited. has not independently confirmed the accuracy of these methods. They are for reference only.

PK studies of PRN1371 in rat, dog, and cynomolgus monkey show rapid iv clearance in all species. PRN1371 shows rapid clearance (Cl=160 mL per min per kg), yet dosing po (20 mg/kg) demonstrates high oral exposure (AUC=4348 h·ng/mL) and a reasonable half-life (t 1/2 =3.8 h). Low levels of pFGFR2 confirms the ability of PRN1371 to block FGFR2 activity in tumor tissue. PRN1371 induces a dose-dependent reduction in tumor volume and up to 68% tumor growth inhibition at the highest dose of 10 mg/kg b.i.d. following 27 days of treatment. All doses are well tolerated with no significant body weight loss. PRN1371 free base has been administered orally once daily as powder in a capsule on a 28-day continuous schedule. Human plasma concentrations for doses ranging from 15 to 35 mg confirm good oral exposure, rapid systemic clearance, no accumulation from day 1 to day 15, and a do

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Brameld KA, et al. Discovery of the Irreversible Covalent FGFR Inhibitor 8-(3-(4-Acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PRN1371) for the Treatment of Solid Tumors. J Med Chem. 2

In Vitro: DMSO : 25 mg/mL (44.53 mM; Need ultrasonic)配制储备液