4FOB
Crystal structure of human anaplastic lymphoma kinase in complex with acyliminobenzimidazole inhibitor 1
Summary for 4FOB
| Entry DOI | 10.2210/pdb4fob/pdb |
| Related | 4FNW 4FNX 4FNY 4FNZ 4FOC 4FOD |
| Descriptor | ALK tyrosine kinase receptor, N-{1-[cis-4-(hydroxymethyl)cyclohexyl]-5-(piperidin-1-ylmethyl)-1H-benzimidazol-2-yl}-3-(prop-2-en-1-ylsulfamoyl)benzamide (3 entities in total) |
| Functional Keywords | receptor tyrosine kinase, inhibitor, crizotinib, neuroblastoma, cd246, phosphotransferase, npm-alk, eml4-alk, in situ proteolysis, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cell membrane; Single-pass type I membrane protein: Q9UM73 |
| Total number of polymer chains | 1 |
| Total formula weight | 40621.70 |
| Authors | Whittington, D.A.,Epstein, L.F.,Chen, H. (deposition date: 2012-06-20, release date: 2012-07-11, Last modification date: 2024-02-28) |
| Primary citation | Lewis, R.T.,Bode, C.M.,Choquette, D.M.,Potashman, M.,Romero, K.,Stellwagen, J.C.,Teffera, Y.,Moore, E.,Whittington, D.A.,Chen, H.,Epstein, L.F.,Emkey, R.,Andrews, P.S.,Yu, V.L.,Saffran, D.C.,Xu, M.,Drew, A.,Merkel, P.,Szilvassy, S.,Brake, R.L. The Discovery and Optimization of a Novel Class of Potent, Selective, and Orally Bioavailable Anaplastic Lymphoma Kinase (ALK) Inhibitors with Potential Utility for the Treatment of Cancer. J.Med.Chem., 55:6523-6540, 2012 Cited by PubMed Abstract: A class of 2-acyliminobenzimidazoles has been developed as potent and selective inhibitors of anaplastic lymphoma kinase (ALK). Structure based design facilitated the rapid development of structure-activity relationships (SAR) and the optimization of kinase selectivity. Introduction of an optimally placed polar substituent was key to solving issues of metabolic stability and led to the development of potent, selective, orally bioavailable ALK inhibitors. Compound 49 achieved substantial tumor regression in an NPM-ALK driven murine tumor xenograft model when dosed qd. Compounds 36 and 49 show favorable potency and PK characteristics in preclinical species indicative of suitability for further development. PubMed: 22734674DOI: 10.1021/jm3005866 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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