6UDX

X-ray co-crystal structure of compound 7 with Mcl-1

6UDX の概要

• エントリーDOI: 10.2210/pdb6udx/pdb
• 関連するPDBエントリー: 6UD2 6UDI 6UDT 6UDU 6UDV
• 分子名称: Induced myeloid leukemia cell differentiation protein Mcl-1, (2R)-[(3S)-6'-chloro-5-(cyclobutylmethyl)-3',4,4',5-tetrahydro-2H,2'H-spiro[1,5-benzoxazepine-3,1'-naphthalen]-7-yl](hydroxy)acetic acid (3 entities in total)
• 機能のキーワード: protein-protein interaction, apoptosis, inhibitor, apoptosis-inhibitor complex, apoptosis/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36728.58

構造登録者

Huang, X. (登録日: 2019-09-19, 公開日: 2019-12-11, 最終更新日: 2024-03-13)

主引用文献

Rescourio, G.,Gonzalez, A.Z.,Jabri, S.,Belmontes, B.,Moody, G.,Whittington, D.,Huang, X.,Caenepeel, S.,Cardozo, M.,Cheng, A.C.,Chow, D.,Dou, H.,Jones, A.,Kelly, R.C.,Li, Y.,Lizarzaburu, M.,Lo, M.C.,Mallari, R.,Meleza, C.,Rew, Y.,Simonovich, S.,Sun, D.,Turcotte, S.,Yan, X.,Wong, S.G.,Yanez, E.,Zancanella, M.,Houze, J.,Medina, J.C.,Hughes, P.E.,Brown, S.P.
Discovery and in Vivo Evaluation of Macrocyclic Mcl-1 Inhibitors Featuring an alpha-Hydroxy Phenylacetic Acid Pharmacophore or Bioisostere.
J.Med.Chem., 62:10258-10271, 2019

PubMed Abstract: Overexpression of the antiapoptotic protein Mcl-1 provides a survival advantage to some cancer cells, making inhibition of this protein an attractive therapeutic target for the treatment of certain types of tumors. Herein, we report our efforts toward the identification of a novel series of macrocyclic Mcl-1 inhibitors featuring an α-hydroxy phenylacetic acid pharmacophore or bioisostere. This work led to the discovery of , a potent Mcl-1 inhibitor (IC = 19 nM in an OPM-2 cell viability assay) with good pharmacokinetic properties and excellent in vivo efficacy in an OPM-2 multiple myeloma xenograft model.

PubMed: 31736296
DOI: 10.1021/acs.jmedchem.9b01310

実験手法

X-RAY DIFFRACTION (1.7 Å)