3ZLO
Crystal structure of BCL-XL in complex with inhibitor (Compound 6)
Summary for 3ZLO
| Entry DOI | 10.2210/pdb3zlo/pdb |
| Related | 3ZK6 3ZLN 3ZLR |
| Descriptor | BCL-2-LIKE PROTEIN 1, 2-[(8E)-8-(1,3-benzothiazol-2-ylhydrazinylidene)-6,7-dihydro-5H-naphthalen-2-yl]-5-(4-phenylbutyl)-1,3-thiazole-4-carboxylic acid (3 entities in total) |
| Functional Keywords | apoptosis, inhibitor |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 21357.63 |
| 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 citation | Lessene, 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: 23603658DOI: 10.1038/NCHEMBIO.1246 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.601 Å) |
Structure validation
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