4TUH

Bcl-xL in complex with inhibitor (Compound 10)

Summary for 4TUH

• Entry DOI: 10.2210/pdb4tuh/pdb
• Descriptor: Bcl-2-like protein 1, 2-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl]-5-{3-[4-(1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenoxy]propyl}-1,3-thiazole-4-carboxylic acid, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: apoptosis, drug design
• Biological source: Homo sapiens (Human); More
• Cellular location: Isoform Bcl-X(L): Mitochondrion inner membrane : Q07817
• Total number of polymer chains: 8
• Total formula weight: 149781.89

Authors

Czabotar, P.E.,Lessense, G.,Smith, B.J.,Colman, P.M. (deposition date: 2014-06-24, release date: 2014-10-15, Last modification date: 2023-12-27)

Primary citation

Koehler, M.F.,Bergeron, P.,Choo, E.F.,Lau, K.,Ndubaku, C.,Dudley, D.,Gibbons, P.,Sleebs, B.E.,Rye, C.S.,Nikolakopoulos, G.,Bui, C.,Kulasegaram, S.,Kersten, W.J.,Smith, B.J.,Czabotar, P.E.,Colman, P.M.,Huang, D.C.,Baell, J.B.,Watson, K.G.,Hasvold, L.,Tao, Z.F.,Wang, L.,Souers, A.J.,Elmore, S.W.,Flygare, J.A.,Fairbrother, W.J.,Lessene, G.
Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.
Acs Med.Chem.Lett., 5:662-667, 2014

PubMed Abstract: Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.

PubMed: 24944740
DOI: 10.1021/ml500030p

Experimental method

X-RAY DIFFRACTION (1.8 Å)