8EL1

Structure of MBP-Mcl-1 in complex with ABBV-467

8EL1 の概要

• エントリーDOI: 10.2210/pdb8el1/pdb
• 関連するPDBエントリー: 8EKX 8EL0
• 分子名称: Maltose/maltodextrin-binding periplasmic protein,Induced myeloid leukemia cell differentiation protein Mcl-1, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, (7R,16R)-19,23-dichloro-10-{[2-(4-{[(2R)-1,4-dioxan-2-yl]methoxy}phenyl)pyrimidin-4-yl]methoxy}-1-(4-fluorophenyl)-20,22-dimethyl-16-[(4-methylpiperazin-1-yl)methyl]-7,8,15,16-tetrahydro-18,21-etheno-13,9-(metheno)-6,14,17-trioxa-2-thia-3,5-diazacyclononadeca[1,2,3-cd]indene-7-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: mbp-mcl-1 fusion protein, apoptosis, inhibitor complex, abbv-467
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 242068.62

構造登録者

Judge, R.A.,Judd, A.S.,Souers, A.J. (登録日: 2022-09-22, 公開日: 2023-10-25, 最終更新日: 2026-03-04)

主引用文献

Yuda, J.,Will, C.,Phillips, D.C.,Abraham, L.,Alvey, C.,Avigdor, A.,Buck, W.,Besenhofer, L.,Boghaert, E.,Cheng, D.,Cojocari, D.,Doyle, K.,Hansen, T.M.,Huang, K.,Johnson, E.F.,Judd, A.S.,Judge, R.A.,Kalvass, J.C.,Kunzer, A.,Lam, L.T.,Li, R.,Martin, R.L.,Mastracchio, A.,Mitten, M.,Petrich, A.,Wang, J.,Ward, J.E.,Zhang, H.,Wang, X.,Wolff, J.E.,Bell-McGuinn, K.M.,Souers, A.J.
Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients.
Commun Med (Lond), 3:154-154, 2023

PubMed Abstract: MCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902).

PubMed: 37880389
DOI: 10.1038/s43856-023-00380-z

実験手法

X-RAY DIFFRACTION (2.406 Å)