6B4U
Crystal structure of MCL-1 in complex with a BIM competitive inhibitor
Summary for 6B4U
| Entry DOI | 10.2210/pdb6b4u/pdb |
| Related | 5VKC 6B4L |
| Descriptor | Induced myeloid leukemia cell differentiation protein Mcl-1, 7-(2-methylphenyl)-1-[2-(morpholin-4-yl)ethyl]-3-{3-[(naphthalen-1-yl)oxy]propyl}-1H-indole-2-carboxylic acid (3 entities in total) |
| Functional Keywords | mcl-1, signaling protein-inhibitor complex, signaling protein, signaling protein/inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Membrane ; Single-pass membrane protein : Q07820 |
| Total number of polymer chains | 1 |
| Total formula weight | 18431.06 |
| Authors | Judge, R.A.,Souers, A.J. (deposition date: 2017-09-27, release date: 2017-10-04, Last modification date: 2024-03-13) |
| Primary citation | Bruncko, M.,Wang, L.,Sheppard, G.S.,Phillips, D.C.,Tahir, S.K.,Xue, J.,Erickson, S.,Fidanze, S.,Fry, E.,Hasvold, L.,Jenkins, G.J.,Jin, S.,Judge, R.A.,Kovar, P.J.,Madar, D.,Nimmer, P.,Park, C.,Petros, A.M.,Rosenberg, S.H.,Smith, M.L.,Song, X.,Sun, C.,Tao, Z.F.,Wang, X.,Xiao, Y.,Zhang, H.,Tse, C.,Leverson, J.D.,Elmore, S.W.,Souers, A.J. Structure-guided design of a series of MCL-1 inhibitors with high affinity and selectivity. J. Med. Chem., 58:2180-2194, 2015 Cited by PubMed Abstract: Myeloid cell leukemia 1 (MCL-1) is a BCL-2 family protein that has been implicated in the progression and survival of multiple tumor types. Herein we report a series of MCL-1 inhibitors that emanated from a high throughput screening (HTS) hit and progressed via iterative cycles of structure-guided design. Advanced compounds from this series exhibited subnanomolar affinity for MCL-1 and excellent selectivity over other BCL-2 family proteins as well as multiple kinases and GPCRs. In a MCL-1 dependent human tumor cell line, administration of compound 30b rapidly induced caspase activation with associated loss in cell viability. The small molecules described herein thus comprise effective tools for studying MCL-1 biology. PubMed: 25679114DOI: 10.1021/jm501258m PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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