7NPY

C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 6-benzyl-N2-methyl-N4-((1S,2S)-2-methylcyclopropyl)pyridine-2,4-dicarboxamide

これはPDB形式変換不可エントリーです。

7NPY の概要

• エントリーDOI: 10.2210/pdb7npy/pdb
• 分子名称: Bromodomain-containing protein 2, ~{N}2-methyl-~{N}4-[(1~{S},2~{S})-2-methylcyclopropyl]-6-(phenylmethyl)pyridine-2,4-dicarboxamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: inhibitor, histone, epigenetic reader, bromodomain, brd2, bromodomain containing protein 2, antagonist, nuclear protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13942.05

構造登録者

Chung, C. (登録日: 2021-02-28, 公開日: 2021-07-21, 最終更新日: 2024-06-19)

主引用文献

Harrison, L.A.,Atkinson, S.J.,Bassil, A.,Chung, C.W.,Grandi, P.,Gray, J.R.J.,Levernier, E.,Lewis, A.,Lugo, D.,Messenger, C.,Michon, A.M.,Mitchell, D.J.,Preston, A.,Prinjha, R.K.,Rioja, I.,Seal, J.T.,Taylor, S.,Wall, I.D.,Watson, R.J.,Woolven, J.M.,Demont, E.H.
Identification of a Series of N -Methylpyridine-2-carboxamides as Potent and Selective Inhibitors of the Second Bromodomain (BD2) of the Bromo and Extra Terminal Domain (BET) Proteins.
J.Med.Chem., 64:10742-10771, 2021

PubMed Abstract: Domain-specific BET bromodomain ligands represent an attractive target for drug discovery with the potential to unlock the therapeutic benefits of antagonizing these proteins without eliciting the toxicological aspects seen with pan-BET inhibitors. While we have reported several distinct classes of BD2 selective compounds, namely, GSK620, GSK549, and GSK046, only GSK046 shows high aqueous solubility. Herein, we describe the lead optimization of a further class of highly soluble compounds based upon a picolinamide chemotype. Focusing on achieving >1000-fold selectivity for BD2 over BD1 ,while retaining favorable physical chemical properties, compound was identified as being 2000-fold selective for BD2 over BD1 (Brd4 data) with >1 mg/mL solubility in FaSSIF media. represents a valuable new ready molecule for the exploration of the BD2 phenotype.

PubMed: 34232650
DOI: 10.1021/acs.jmedchem.0c02155

実験手法

X-RAY DIFFRACTION (1.601 Å)