1Z5M
Crystal Structure Of N1-[3-[[5-bromo-2-[[3-[(1-pyrrolidinylcarbonyl)amino]phenyl]amino]-4-pyrimidinyl]amino]propyl]-2,2-dimethylpropanediamide Complexed with Human PDK1
Summary for 1Z5M
| Entry DOI | 10.2210/pdb1z5m/pdb |
| Related | 1h1w 1uu7 1uu8 1uu9 1uvr |
| Descriptor | 3-phosphoinositide dependent protein kinase-1, SULFATE ION, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | protein inhibitor complex, serine kinase, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: O15530 |
| Total number of polymer chains | 1 |
| Total formula weight | 34085.36 |
| Authors | Whitlow, M.,Adler, M. (deposition date: 2005-03-18, release date: 2005-04-19, Last modification date: 2024-10-30) |
| Primary citation | Feldman, R.I.,Wu, J.M.,Polokoff, M.A.,Kochanny, M.J.,Dinter, H.,Zhu, D.,Biroc, S.L.,Alicke, B.,Bryant, J.,Yuan, S.,Buckman, B.O.,Lentz, D.,Ferrer, M.,Whitlow, M.,Adler, M.,Finster, S.,Chang, Z.,Arnaiz, D.O. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J.Biol.Chem., 280:19867-19874, 2005 Cited by PubMed Abstract: The phosphoinositide 3-kinase/3-phosphoinositide-dependent kinase 1 (PDK1)/Akt signaling pathway plays a key role in cancer cell growth, survival, and tumor angiogenesis and represents a promising target for anticancer drugs. Here, we describe three potent PDK1 inhibitors, BX-795, BX-912, and BX-320 (IC(50) = 11-30 nm) and their initial biological characterization. The inhibitors blocked PDK1/Akt signaling in tumor cells and inhibited the anchorage-dependent growth of a variety of tumor cell lines in culture or induced apoptosis. A number of cancer cell lines with elevated Akt activity were >30-fold more sensitive to growth inhibition by PDK1 inhibitors in soft agar than on tissue culture plastic, consistent with the cell survival function of the PDK1/Akt signaling pathway, which is particularly important for unattached cells. BX-320 inhibited the growth of LOX melanoma tumors in the lungs of nude mice after injection of tumor cells into the tail vein. The effect of BX-320 on cancer cell growth in vitro and in vivo indicates that PDK1 inhibitors may have clinical utility as anticancer agents. PubMed: 15772071DOI: 10.1074/jbc.M501367200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.17 Å) |
Structure validation
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