CYP4A11/CYP4F2-IN-2

CYP4A11/CYP4F2-IN-2 is a potent and orally active dual inhibitor of cytochrome P450 (CYP) 4A11 and CYP4F2, with IC50s of 140 nM and 40 nM, respectively. CYP4A11/CYP4F2-IN-2 has potential for the research of renal diseases[1].

Signaling Pathways >> Metabolic Enzyme/Protease >> Cytochrome P450

Research Areas >> Metabolic Disease

CYP4A11:140 nM (IC50)

CYP4F2:40 nM (IC50)

CYP4A11/CYP4F2-IN-2 (compound 11c) inhibits 20-Hydroxyeicosatetraenoic acid (20-HETE) production from arachidonic acid in human renal microsomes, with an IC50 of 29 nM[1].

CYP4A11/CYP4F2-IN-2 (compound 11c) (0.03-1 mg/kg; a single p.o.) inhibits renal 20-HETE production of rats in a dose-dependent manner[1]. CYP4A11/CYP4F2-IN-2 (0.5 mg/kg; i.v.) exhibits low CL (1430 mL/h/kg), moderate Vdss(763 mL/kg), and short T1/2 (0.424 h) in mice[1]. CYP4A11/CYP4F2-IN-2 (1 mg/kg; i.v.) exhibits low CL (226 mL/h/kg), moderate Vdss(839 mL/kg), and T1/2 (3.01 h) in SD rats[1]. CYP4A11/CYP4F2-IN-2 (1 mg/kg; p.o.) exhibits Cmax (623 ng/mL), T1/2 (3.03 h), and high bioavailability (97.7%) in SD rats[1].

[1]. Kawamura M, et, al. Discovery of Novel Pyrazolylpyridine Derivatives for 20-Hydroxyeicosatetraenoic Acid Synthase Inhibitors with Selective CYP4A11/4F2 Inhibition. J Med Chem. 2022 Nov 10;65(21):14599-14613.