FGFR2/3-IN-1

Names

[ CAS No. ]:
2640352-86-7

[ Name ]:
FGFR2/3-IN-1

Biological Activity

[Description]:

FGFR2/3-IN-1 is a potent and selective FGFR2 and FGFR3 (FGFR) inhibitor with IC50s of 1 nM and 0.5 nM, respectively. FGFR2/3-IN-1 displays >40-fold selectivity over FGFR1/FGFR4 and other kinome. FGFR2/3-IN-1 also inhibits FGFR3 V555L and V555M mutants with IC50s of 2.7 nM and 6.1 nM, respectively[1].

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR

[Target]

FGFR2:1 nM (IC50)

FGFR3:0.5 nM (IC50)

FGFR3 V555L:2.7 nM (IC50)

FGFR3 V555M:6.1 nM (IC50)

FGFR1:21 nM (IC50)

FGFR4:145 nM (IC50)


[In Vitro]

FGFR2/3-IN-1 (compound 29) has a clean CYP profile (CYP3A4 IC50 >25 μM). FGFR2/3-IN-1 displays excellent potency (whole blood, IC50 = 177 nM) in a whole blood (WB) assay[1].

[In Vivo]

FGFR2/3-IN-1 (compound 29) is advanced into rat pharmacokinetics studies. Clearance in the i.v. arm is low (hepatic blood flow (HBF) = 35%), with a moderate half-life (t1/2 = 1.7 h). In the p.o. dose, FGFR2/3-IN-1 demonstrates good exposure (AUC = 5108 nM·h) and high oral bioavailability (F% = 82)[2]. rat i.v. rat p.o. dose (mg/kg) 1.0 dose (mg/kg) 3.0 HBF% 35 Cmax (nM) 2303 Vdss (L/kg) 1.6 AUC (nM·h) 5108 T1/2 (h) 1.7 F% 82

[References]

[1]. Artem Shvartsbart, et al. Discovery of Potent and Selective Inhibitors of Wild-Type and Gatekeeper Mutant Fibroblast Growth Factor Receptor (FGFR) 2/3. J Med Chem. 2022 Nov 24;65(22):15433-15442.  

Chemical & Physical Properties

[ Molecular Formula ]:
C23H22D3N7O3

[ Molecular Weight ]:
450.51

Related Compounds