Infigratinib phosphate (BGJ-398 phosphate; NVP-BGJ398 phosphate) is a potent inhibitor of theFGFRfamily withIC₅₀of 0.9 nM, 1.4 nM, 1 nM, and 60 nM forFGFR1,FGFR2,FGFR3, andFGFR4, respectively.

Infigratinib phosphate inhibits FGFR1, FGFR2, and FGFR3 with IC₅₀=~1 nM, FGFR3^K650Ewith IC₅₀=4.9 nM, and FGFR4 with IC₅₀=60 nM. IC₅₀values for all other kinases are in the μM range (FYN, LCK, YES, and ABL, IC₅₀=1.9, 2.5, 1.1, and 2.3 μM, respectively) except for VEGFR2, KIT, and LYN, which are inhibited at submicromolar concentrations (IC₅₀=0.18, 0.75, and 0.3 μM, respectively). Infigratinib inhibits the proliferation of the FGFR1-, FGFR2-, and FGFR3-dependent BaF3 cells with IC₅₀values which are in the low nanomolar range and comparable to those observed for the inhibition of the receptors kinase activity in the enzymatic assay. For the remaining cells, all IC₅₀values are greater than 1.5 μM except for VEGFR2 (IC₅₀1449 and 938 nM), for which there is at least a 400-fold selectivity versus FGFR1, FGFR2, and FGFR3^[1]. Infigratinib (ranging between 1 nM and 10 μM) is potent at inhibiting cell growth ofFGFR2-mutant endometrial cancer cells^[2].

Infigratinib is administered to athymic nude mice implanted subcutaneously with RT112/luc1 tumors: either as a 5 mg/kg intravenous bolus in NMP/PEG200 (1:9, v/v) or orally by gavage as a suspension in PEG300/D5W (2:1, v/v) at a 20 mg/kg dose. The relevant pharmacokinetic (PK) parameters indicate that the oral bioavailability of Infigratinib in this study is 32%. After intravenous dosing, Infigratinib shows a rapid distribution from the vascular compartment into the peripheral tissues, translating into a high volume of distribution (26 L/kg). The plasma clearance is high at 3.3 L/h/kg (61% of liver blood flow). The ratio of tumor to plasma after oral dosing based on AUC is determined to be 10^[1]. Infigratinib (30 mg/kg) significantly inhibits the growth ofFGFR2-mutated endometrial cancer xenograft models^[2].

658.47

Solid

C₂₆H₃₄Cl₂N₇O₇P

1310746-10-1

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

DMSO : ≥ 12.5 mg/mL(18.98 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。