6ALC

CREBBP bromodomain in complex with Cpd 4 (1-(1-(cyclopropylmethyl)-3-(1H-indol-4-yl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)ethan-1-one)

Summary for 6ALC

• Entry DOI: 10.2210/pdb6alc/pdb
• Related: 6ALB
• Descriptor: CREB-binding protein, DIMETHYL SULFOXIDE, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: crebbp, bromodomain, small molecule inhibitor, protein binding-inhibitor complex, protein binding/inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 27565.55

Authors

Murray, J.M. (deposition date: 2017-08-07, release date: 2018-08-08, Last modification date: 2023-10-04)

Primary citation

Lai, K.W.,Romero, F.A.,Tsui, V.,Beresini, M.H.,de Leon Boenig, G.,Bronner, S.M.,Chen, K.,Chen, Z.,Choo, E.F.,Crawford, T.D.,Cyr, P.,Kaufman, S.,Li, Y.,Liao, J.,Liu, W.,Ly, J.,Murray, J.,Shen, W.,Wai, J.,Wang, F.,Zhu, C.,Zhu, X.,Magnuson, S.
Design and synthesis of a biaryl series as inhibitors for the bromodomains of CBP/P300.
Bioorg. Med. Chem. Lett., 28:15-23, 2018

PubMed Abstract: A novel, potent, and orally bioavailable inhibitor of the bromodomain of CBP, compound 35 (GNE-207), has been identified through SAR investigations focused on optimizing al bicyclic heteroarene to replace the aniline present in the published GNE-272 series. Compound 35 has excellent CBP potency (CBP IC = 1 nM, MYC EC = 18 nM), a selectively index of >2500-fold against BRD4(1), and exhibits a good pharmacokinetic profile.

PubMed: 29169673
DOI: 10.1016/j.bmcl.2017.11.025

Experimental method

X-RAY DIFFRACTION (1.391 Å)