Infigratinib phosphate (BGJ-398 phosphate) is an effective inhibitor of the FGFR family (IC50: 0.9 nM, 1.4 nM, 1 nM, and 60 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively).

Infigratinib inhibits the proliferation of the FGFR1-, FGFR2-, and FGFR3-dependent BaF3 cells with IC50 values which are in the low nanomolar range and comparable to those observed for the inhibition of the receptors kinase activity in the enzymatic assay. Infigratinib phosphate suppresses FGFR1, FGFR2, and FGFR3(IC50=~1 nM), FGFR3K650E(IC50=4.9 nM), and FGFR4(IC50=60 nM). IC50 values 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 (ranging between 1 nM and 10 μM) is effective at inhibiting cell growth of FGFR2-mutant endometrial cancer cells. For the remaining cells, all IC50 values are greater than 1.5 μM except for VEGFR2 (IC50 1449 and 938 nM), for which there is at least a 400-fold selectivity versus FGFR1, FGFR2, and FGFR3[1][2].

Infigratinib, at a dosage of 30 mg/kg, effectively inhibits the proliferation of FGFR2-mutated endometrial cancer in xenograft models using athymic nude mice. The compound is administered either as a 5 mg/kg intravenous injection in NMP/PEG200 (1:9, v/v) or orally at 20 mg/kg in a PEG300/D5W (2:1, v/v) mixture. Following intravenous administration, Infigratinib quickly disperses from the bloodstream to peripheral tissues, evidenced by a high distribution volume (26 L/kg). Pharmacokinetic studies reveal that its oral bioavailability is 32%, with a significant plasma clearance rate of 3.3 L/h/kg, approximately 61% of liver blood flow. The drug concentration in tumors relative to plasma, based on the Area Under the Curve (AUC) ratio, is 10 after oral administration, indicating significant efficacy in targeting tumor cells.