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3ZLN

Crystal structure of BCL-XL in complex with inhibitor (Compound 3)

Summary for 3ZLN
Entry DOI10.2210/pdb3zln/pdb
Related3ZK6 3ZLO 3ZLR
DescriptorBCL-2-LIKE PROTEIN 1, 6-[(8E)-8-(1,3-benzothiazol-2-ylhydrazinylidene)-6,7-dihydro-5H-naphthalen-2-yl]pyridine-2-carboxylic acid, SULFATE ION, ... (5 entities in total)
Functional Keywordsapoptosis, inhibitor
Biological sourceHOMO SAPIENS (HUMAN)
Total number of polymer chains1
Total formula weight21625.80
Authors
Czabotar, P.E.,Lessene, G.L.,Smith, B.J.,Colman, P.M. (deposition date: 2013-02-04, release date: 2013-04-24, Last modification date: 2023-12-20)
Primary citationLessene, G.L.,Czabotar, P.E.,Sleebs, B.E.,Zobel, K.,Lowes, K.L.,Adams, J.M.,Baell, J.B.,Colman, P.M.,Deshayes, K.,Fairbrother, W.J.,Flygare, J.A.,Gibbons, P.,Kersten, W.J.A.,Kulasegaram, S.,Moss, R.M.,Parisot, J.P.,Smith, B.J.,Street, I.P.,Yang, H.,Huang, D.C.S.,Watson, K.G.
Structure-Guided Design of a Selective Bcl-Xl Inhibitor
Nat.Chem.Biol., 9:390-397, 2013
Cited by
PubMed Abstract: The prosurvival BCL-2 family protein BCL-X(L) is often overexpressed in solid tumors and renders malignant tumor cells resistant to anticancer therapeutics. Enhancing apoptotic responses by inhibiting BCL-X(L) will most likely have widespread utility in cancer treatment and, instead of inhibiting multiple prosurvival BCL-2 family members, a BCL-X(L)-selective inhibitor would be expected to minimize the toxicity to normal tissues. We describe the use of a high-throughput screen to discover a new series of small molecules targeting BCL-X(L) and their structure-guided development by medicinal chemistry. The optimized compound, WEHI-539 (7), has high affinity (subnanomolar) and selectivity for BCL-X(L) and potently kills cells by selectively antagonizing its prosurvival activity. WEHI-539 will be an invaluable tool for distinguishing the roles of BCL-X(L) from those of its prosurvival relatives, both in normal cells and notably in malignant tumor cells, many of which may prove to rely upon BCL-X(L) for their sustained growth.
PubMed: 23603658
DOI: 10.1038/NCHEMBIO.1246
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.288 Å)
Structure validation

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