RG7800 hydrochloride 是一种可口服的 SMN2 剪接调节剂，对 SMN2 剪接及 SMN 蛋白的 EC1.5x 值分别为 23 nM 和 87 nM。
货号:ajcx14104
CAS:N/A
分子式:C24H28N6O.xHCl
分子量：N/A
溶解度:H2O: ≥ 113.5 mg/mL
纯度：98%
存储：Store at -20°C
库存：现货

Background:

RG7800 hydrochloride is an orally active SMN2 splicing modulator, with EC1.5xs of 23 nM and 87 nM for SMN2 splicing and SMN protein; RG7800 hydrochloride has the potential to treat spinal muscular atrophy. EC1.5x: 23 nM (SMN2 splicing), 87 nM (SMN protein)[1]

RG7800 hydrochloride is an orally active SMN2 splicing modulator, with EC1.5xs of 23 nM and 87 nM for SMN2 splicing and SMN protein; and is the first small molecule SMN2 splicing modifier to enter human clinical trials[1].

RG7800 is a favorable agent metabolism and pharmacokinetic (DMPK) profile in the rat and in cynomolgus monkey with good oral bioavailability. RG7800 (1, 3, 10 mg/kg, p.o.) dose-dependently elevates the SMN protein level in the brain and in peripheral tissue of δ7 mice[1].

[1]. Ratni H, et al. Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy. J Med Chem. 2016 Jul 14;59(13):6086-100.

Protocol:

Animal experiment:

Mice[1]Homozygous Δ7 mice are dosed ip with RG7800 or vehicle (100% DMSO, 2.5 mL/kg) once per day from PND3 through postnatal day 3 (PND23), and the dosing regimen is switched on PND24 to a 3-fold higher oral dose once daily in 0.5% HPMC and 0.1% Tween 80. Litters are randomized across groups. Body weight and survival are assessed daily. Survival analysis is done using GraphPad Prism (log-rank test), and a p<0.05 is considered as significant[1].

参考文献: [1]. Ratni H, et al. Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy. J Med Chem. 2016 Jul 14;59(13):6086-100.