L-Moses (L-45) dihydrochloride is the first potent, selective, and cell-active p300/CBP-associated factor (PCAF) bromodomain (Brd) inhibitor with a K_d of 126 nM.

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).

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Moustakim M, et al. Discovery of a PCAF Bromodomain Chemical Probe. Angew Chem Int Ed Engl. 2017 Jan 16;56(3):827-831.  [Content Brief]