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L-Moses dihydrochloride

CAS No. :

MCE 站：L-Moses dihydrochloride

产品活性：L-Moses (L-45) dihydrochloride 是一个有效的选择性 p300/CBP 相关因子 (PCAF) 溴结构域 (Brd) 抑制剂，K_d 为 126 nM。

研究领域：Epigenetics

作用靶点：Epigenetic Reader Domain

In Vitro: L-Moses (L-45) disrupts PCAF-Brd histone H3.3 interaction in cells using a nanoBRET assay, ａnd a co-crystal structure of L-Moses with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF ａnd GCN5 bromodomains. A structure using highly homologous (64 % identity) Brd from Plasmodium falciparum, PfGCN5, of which L-Moses is also a potent ligand (isothermal titration calorimetry (ITC) KD 280 nM), is successfully obtained (PDB: 5TPX). L-Moses binds in the acetylated lysines (KAc) -binding pocket of PfGCN (blue ribbon ａnd sticks) ａnd makes H-bonds (dotted lines) through the triazole to N1436 ａnd the first of a network of four water molecules (red spheres).

In Vivo: L-Moses (L-45) shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell-permeability, ａnd metabolic stability in human ａnd mouse liver microsomes, supporting its potential for in vivo use.

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