5K00

MELK in complex with NVS-MELK5

Summary for 5K00

• Entry DOI: 10.2210/pdb5k00/pdb
• Descriptor: Maternal embryonic leucine zipper kinase, 4-{2-[(3-methoxyphenyl)amino]-4-[(piperidin-4-yl)methoxy]pyrimidin-5-yl}-N-[2-oxo-2-(phenylamino)ethyl]benzamide (3 entities in total)
• Functional Keywords: kinase uba typeii inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane ; Peripheral membrane protein : Q14680
• Total number of polymer chains: 1
• Total formula weight: 39525.73

Authors

Sprague, E.R. (deposition date: 2016-05-17, release date: 2017-03-01, Last modification date: 2024-03-06)

Primary citation

Chen, X.,Giraldes, J.,Sprague, E.R.,Shakya, S.,Chen, Z.,Wang, Y.,Joud, C.,Mathieu, S.,Chen, C.H.,Straub, C.,Duca, J.,Hurov, K.,Yuan, Y.,Shao, W.,Toure, B.B.
"Addition" and "Subtraction": Selectivity Design for Type II Maternal Embryonic Leucine Zipper Kinase Inhibitors.
J. Med. Chem., 60:2155-2161, 2017

PubMed Abstract: While adding the structural features that are more favored by on-target activity is the more common strategy in selectivity optimization, the opposite strategy of subtracting the structural features that contribute more to off-target activity can also be very effective. Reported here is our successful effort of improving the kinase selectivity of type II maternal embryonic leucine zipper kinase inhibitors by applying these two complementary approaches together, which clearly demonstrates the powerful synergy between them.

PubMed: 28186750
DOI: 10.1021/acs.jmedchem.7b00033

Experimental method

X-RAY DIFFRACTION (1.77 Å)