BI-749327 

BI-749327 is a potent, high selectivity and orally bioavailable TRPC6 antagonist, with IC₅₀s of 13 nM, 19 nM and 15 nM for mouse, human and guinea pig TRPC6, respectively. BI-749327 is 85-fold more selective for mouse TRPC6 than TRPC3 and 42-fold versus TRPC7^[1].

IC50: 13 nM (mouse TRPC6), 19 nM (human TRPC6), 15 nM (guinea pig TRPC6)^[1]

BI-749327 suppresses NFAT activation in HEK293T cells expressing wild-type or gain-of-function TRPC6 mutants and blocks associated signaling and expression of prohypertrophic genes in isolated myocytes^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

BI-749327 (30 mg/kg/day; i.g.) improves left heart function, reduces volume/mass ratio, and blunts expression of profibrotic genes and interstitial fibrosis in mice subjected to sustained pressure overload^[1].
BI-749327 dose dependently reduces renal fibrosis and associated gene expression in mice with unilateral ureteral obstruction^[1].
BI-749327 has long terminal half-life (t_1/2 8.5-13.5 hours) for mice (3-30 mg/kg; p.o.)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

442.43

Solid

C₂₃H₂₁F₃N₄O₂

2361241-23-6

NC1=NN=C(C2CCN(C(C3=CC=C(OC4=CC=C(C(F)(F)F)C=C4)C=C3)=O)CC2)C=C1

Room temperature in continental US; may vary elsewhere.

• [1]. Lin B L, et al. In vivo selective inhibition of TRPC6 by antagonist BI 749327 ameliorates fibrosis and dysfunction in cardiac and renal disease. Proc Natl Acad Sci U S A. 2019 May 14;116(20):10156-10161.  [Content Brief]