L-45

Research use only, not for human use.

PCAF BRD inhibitor L-45 is a potent, selective, and cell-active PCAF bromodomain inhibitor with Ki of 47 nM in HTRF assays.

PCAF BRD inhibitor L-45 is a potent, selective, and cell-active PCAF bromodomain inhibitor with Ki of 47 nM in HTRF assays, >4,500-fold selectivity over BRD4; disrupt PCAF-Brd histone H3.3 interaction in cells using a nanoBRET assay, shows high selectivity for PCAF and GCN5 bromodomain (Kd=600 nM); shows no observable cytotoxicity in PBMCs, good cell-permeability, and metabolic stability in human and mouse liver microsomes.

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).

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.

PCAF BRD inhibitor L-45

Chromatin/Epigenetic

Bromodomain

Bromodomain

Cancer

——

2079885-05-3

360.465

C21H24N6

>98% (HPLC)

In Vitro:?DMSO : 33.33 mg/mL (92.47 mM)

C[C@H](NC(C1=C2C=CC=C1)=NN3C2=NN=C3C)[C@H](C4=CC=CC=C4)N(C)C

(1S,2S)-N1,N1-dimethyl-N2-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)-1-phenylpropane-1,2-diamine

(-20℃)

With Ice Pack

≥ 2 years