BI-749327

Product NameBI-749327
CAS2361241-23-6
MFC23H21F3N4O2
MW442.43
EINECS
MOL File2361241-23-6.mol

Chemical Properties

Boiling point	637.5±55.0 °C(Predicted)
Density	1.334±0.06 g/cm3(Predicted)
storage temp.	-20°C
solubility	Soluble in DMSO (25 mg/ml)
form	solid
pka	5.26±0.10(Predicted)
color	White
Stability	Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.

Usage And Synthesis

Description

BI 749327 (2361241-23-6) is a potent (IC50 = 13 nM mouse TRPC6, 19 nM human TRPC6) and selective (85-fold over TRPC3, 42-fold over TRC7) orally available blocker of TRPC6.1 It suppressed interstitial fibrosis and associated molecular signaling in mouse heart and kidney disease models. BI 749327 reversed established pulmonary hypertension by 50% via regression of pulmonary remodeling in a mouse model.2

Uses

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].

in vivo

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].

Animal Model:	C57BL/6J mice^[1]
Dosage:	30 mg/kg/day
Administration:	Oral gavage
Result:	Improved left heart function, reduced volume/mass ratio, and blunted expression of profibrotic genes and interstitial fibrosis in mice subjected to sustained pressure overload.

Animal Model:	CD-1 mice^[1]
Dosage:	3 mg/kg, 10 mg/kg, 30 mg/kg
Administration:	Oral administration
Result:	t_1/2 8.5-13.5 hours

References

[1] BRIAN LEEI LIN. In vivo selective inhibition of TRPC6 by antagonist BI 749327 ameliorates fibrosis and dysfunction in cardiac and renal disease.[J]. ACS Catalysis , 2019: 10156-10161. DOI:10.1073/pnas.1815354116
[2] PRITESH P JAIN. TRPC6, a therapeutic target for pulmonary hypertension.[J]. ACS Applied Electronic Materials, 2021: L1161-L1182. DOI:10.1152/ajplung.00159.2021

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