| Identification | Back Directory | [Name]
BI-749327 | [CAS]
2361241-23-6 | [Synonyms]
BI-749327
Methanone, [4-(6-amino-3-pyridazinyl)-1-piperidinyl][4-[4-(trifluoromethyl)phenoxy]phenyl]- | [Molecular Formula]
C23H21F3N4O2 | [MDL Number]
MFCD32062737 | [MOL File]
2361241-23-6.mol | [Molecular Weight]
442.43 |
| Chemical Properties | Back Directory | [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. |
| Hazard Information | Back Directory | [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 (t1/2 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: | t1/2 8.5-13.5 hours |
| [References]
Lin et al. (2019) In vivo selective inhibition of TRPC6 by antagonist BI 749327 ameliorates fibrosis and dysfunction in cardiac and renal disease; Proc. Natl. Acad. Sci. USA 116 10156
Jain et al. (2021) TRPC6, a therapeutic target for pulmonary hypertension; Am. J. Physiol. Lung Cell. Mol. Physiol. 321 L1161 |
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| Company Name: |
BOC Sciences
|
| Tel: |
1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
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