Infigratinib phosphate

SKU: orb1706892

Description

Infigratinib phosphate is a potent and selective small-molecule inhibitor of fibroblast growth factor receptors (FGFRs), demonstrating low nanomolar IC50 values against FGFR1-3. It is widely used in preclinical research to investigate FGFR-driven signaling in vitro and has shown antitumor efficacy in vivo models of various cancers.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1310746-10-1
• MW: 658.47
• Purity: 99.60% (May vary between batches)
• Formula: C₂₆H₃₄Cl₂N₇O₇P
• SMILES: O=C(NC=1C(Cl)=C(OC)C=C(OC)C1Cl)N(C=2N=CN=C(C2)NC3=CC=C(C=C3)N4CCN(CC)CC4)C.O=P(O)(O)O
• Target: FGFR
• Solubility: DMSO:11.7 mg/mL (17.77 mM)

Bioactivity

• Target IC50:
  FGFR1:0.9 nM|FGFR4:60 nM|FGFR3:1 nM|FGFR2:1.4 nM
• In Vivo:
  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.
• In Vitro:
  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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

NVP-BGJ 398 Phosphate, NVP-BGJ398 Phosphate, NVP-BGJ398 phosphate, NVP-BGJ-398 Phosphate, Infigratinib Phosphate, FGFR2, FGFR1, FGFR3, FGFR4, BGJ 398 Phosphate, BGJ398 Phosphate, BGJ-398 Phosphate, BGJ-398 phosphate

Compound Identifiers

PubChem CID

56669626