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RG2833

CAS No. : 1215493-56-3

MCE 国际站：RG2833

产品活性：RG2833 是一种可透过血脑屏障的 HDAC 抑制剂，抑制 HDAC1 和 HDAC3 的活性，IC₅₀ 值分别为 60 nM 和 50 nM，K_i 值分别为 32 和 5 nM。

研究领域：Cell Cycle/DNA Damage  |  Epigenetics

作用靶点：HDAC

In Vitro: The K_i values of RG2833 for HDAC1 and HDAC3 are 32 nM and 5 nM, respectively. RG2833 is highly active in the whole tested concentration range from 1 to 10 µM. Continuous incubation with RG2833 slows the increase in frataxin protein, and when the compound is removed, frataxin protein levels rapidly increased in the cells from patient P13. RG2833 produces significant increases in brain aconitase enzyme activity, together with reduction of neuronal pathology of the dorsal root ganglia (DRG).

In Vivo: RG2833 (150 mg/kg) is able to correct frataxin deficiency in the brain and heart of KIKI mice 24 hours after a single injection, but not when lower doses are used. When followed in time, the frataxin mRNA increase induced by RG2833 in the KIKI mouse can be first detected at 12 hours and reach a maximum at 24 hours in both brain and heart. RG2833 (100 mg/kg, s.c.) is well tolerated in chronic dosing of mice without toxicity. RG2833 improves motor coordination of YG8R FRDA mice. RG2833 increases frataxin protein expression in the brain of YG8R FRDA mice. RGFP109 (30 mg/kg, p.o. once daily for 6 days) has no acute effects on dyskinesia after single or 6 days once-daily treatment. One week following cessation of RGFP109, dyskinesia and duration of ON-time with disabling dyskinesia are reduced by 37% and 50%, respectively.

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