BMN 349 (Crovozalpon, BMN349) | Z α1-antitrypsin polymerisation inhibitor

Chemical Structure : BMN 349

BMN 349 (Crovozalpon, BMN349, BMN-349)

Catalog No.: PC-25037Not For Human Use, Lab Use Only.

BMN 349 (Crovozalpon, BMN349) is a specific small molecule inhibitor of Z mutant alpha-1 antitrypsin (Z-AAT) polymerization that preferentially binds Z-AAT and blocks polymerization.

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Biological Activity

BMN 349 (Crovozalpon, BMN349) is a specific small molecule inhibitor of Z mutant alpha-1 antitrypsin (Z-AAT) polymerization that preferentially binds Z-AAT and blocks polymerization.

BMN 349 binds human plasma Z-AAT ~150 times faster than human plasma M-AAT, with calculated kapp of 2.49 ×104 M−1 s−1 and 1.59 ×102 M−1 s−1 for Z- and M-AAT, respectively.

BMN 349 reduces polymerization and increases secretion of Z-AAT in Tet-inducible CHO cell model expressing Z-AAT.

BMN 349 induces dose-dependent increase in total Z-AAT (EC50=0.91 μM) and a decrease in polymeric Z-AAT (EC50=1.57 μM) at the 48-hour time point in CHO-K1-Tet-Z-AAT cells.

BMN 349 binds to a cryptic pocket in alpha-1 antitrypsin (AAT).

( 20 mg/kg/day and 60 mg/kg/day, oral gavage) treatment results dose-dependent increases in total plasma Z-AAT and a concurrent decrease in circulating and liver Z-AAT polymers.

BMN 349 (Crovozalpon) decrease in circulating and liver Z-AAT polymers in mouse models of human AAT deficiency (AATD) associated liver disease.

BMN 349 rapidly and potently inhibits hepatic Z-AAT polymerization and accumulation, thereby enhancing Z-AAT secretion and improving overall liver health in PiZ mice.

Physicochemical Properties

M.Wt	408.83
Formula	C20H19ClF2N2O3
Appearance	Solid
CAS No.
Storage	Solide Powder -20°C 12 Months; 4°C 6 Months	In Solvent -80°C 6 Months; -20°C 6 Months
Shipping
Solubility	10 mM in DMSO
Chemical Name/SMILES	N-((1S,2R)-1-(2-chloro-3-fluorophenyl)-1-hydroxypentan-2-yl)-7-fluoro-2-oxoindoline-4-carboxamide

References

1. Patent WO2025049912 A1.; 2. Handyside B, et al. Hepatology. 2026 May 1. doi: 10.1097/HEP.0000000000001778.

BMN 349 (Crovozalpon, BMN349, BMN-349)

Biological Activity

Physicochemical Properties

References

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