7NPY
C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 6-benzyl-N2-methyl-N4-((1S,2S)-2-methylcyclopropyl)pyridine-2,4-dicarboxamide
This is a non-PDB format compatible entry.
Summary for 7NPY
| Entry DOI | 10.2210/pdb7npy/pdb |
| Descriptor | 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) |
| Functional Keywords | inhibitor, histone, epigenetic reader, bromodomain, brd2, bromodomain containing protein 2, antagonist, nuclear protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 13942.05 |
| Authors | Chung, C. (deposition date: 2021-02-28, release date: 2021-07-21, Last modification date: 2024-06-19) |
| Primary citation | 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 Cited by 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: 34232650DOI: 10.1021/acs.jmedchem.0c02155 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.601 Å) |
Structure validation
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