VX-765

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

VX-765 (Belnacasan) 是 VRT-043198 的口服吸收前药，VRT-043198 是白细胞介素转换酶/caspase-1 的有效选择性抑制剂，Ki 为 0.8 nM。

VX-765 (Belnacasan) is an orally absorbed prodrug of VRT-043198, which is a potent and selective inhibitor of interleukin-converting enzyme/caspase-1 with Ki of 0.8 nM; VRT-043198 exhibits 100- to 10,000-fold selectivity against other caspase-3 and -6 to -9, VX-765 is converted rapidly to VRT-043198 under the action of plasma and liver esterases; inhibits LPS-induced IL-1β production, reduces disease severity and the expression of inflammatory mediators in models of rheumatoid arthritis and skin inflammation.Epilepsy Phase 2 Discontinued(In Vivo):Belnacasan reduces inflammatory response in murine models of inflammatory disease.Belnacasan (50-200 mg/kg) significantly reduces serum IL-1β levels by as much as 60%. It is noteworthy that the effect of Belnacasan on the release of IL-1β induced by LPS reached a plateau at 100 mg/kg. Belnacasan (25-100 mg/kg × 2) significantly reduces ear edema. Belnacasan also dose-dependently reduces the concentrations of cytokines, chemokines, and inflammatory mediators in the ear biopsy samples.Belnacasan (25-200 mg/kg) significantly delays the time to seizure onset by 1.5- to twofold (p<0.01), reduces the number of seizures by 40% (p<0.01) and the total time spent in EEG seizure activity by 30 to 50% (p<0.01).

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Belnacasan reduces inflammatory response in murine models of inflammatory disease.Belnacasan (50-200 mg/kg) significantly reduces serum IL-1β levels by as much as 60%. It is noteworthy that the effect of Belnacasan on the release of IL-1β induced by LPS reached a plateau at 100 mg/kg. Belnacasan (25-100 mg/kg × 2) significantly reduces ear edema. Belnacasan also dose-dependently reduces the concentrations of cytokines, chemokines, and inflammatory mediators in the ear biopsy samples. Belnacasan (25-200 mg/kg) significantly delays the time to seizure onset by 1.5- to twofold (p<0.01), reduces the number of seizures by 40% (p<0.01) and the total time spent in EEG seizure activity by 30 to 50% (p<0.01).

Belnacasan | VX765 | VX 765

Apoptosis

Caspase

Caspase-1|Caspase-4

Neurological Disease

Epilepsy

273404-37-8

508.995

C24H33ClN4O6

>98% (HPLC)

DMSO: ≥ 27 mg/mL

O=C([C@H]1N(C([C@@H](NC(C2=CC=C(N)C(Cl)=C2)=O)C(C)(C)C)=O)CCC1)N[C@@H](C3)[C@H](OCC)OC3=O

L-Prolinamide, N-(4-amino-3-chlorobenzoyl)-3-methyl-L-valyl-N-[(2R,3S)-2-ethoxytetrahydro-5-oxo-3-furanyl]-

(-20℃)

With Ice Pack

≥ 2 years