5V24

Structure-based drug design of novel ASK1 inhibitors using a fully integrated lead optimization strategy

Summary for 5V24

• Entry DOI: 10.2210/pdb5v24/pdb
• Related: 5V19
• Descriptor: Mitogen-activated protein kinase kinase kinase 5, 2-[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]-N-(pyridin-2-yl)-1,3-thiazole-4-carboxamide (3 entities in total)
• Functional Keywords: transferase, metal-binding, apoptosis, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q99683
• Total number of polymer chains: 2
• Total formula weight: 61648.53

Authors

Dougan, D.R.,Lawson, J.D. (deposition date: 2017-03-02, release date: 2017-03-29, Last modification date: 2024-03-06)

Primary citation

Gibson, T.S.,Johnson, B.,Fanjul, A.,Halkowycz, P.,Dougan, D.R.,Cole, D.,Swann, S.
Structure-based drug design of novel ASK1 inhibitors using an integrated lead optimization strategy.
Bioorg. Med. Chem. Lett., 27:1709-1713, 2017

PubMed Abstract: Structure-based drug design is an iterative process that is an established means to accelerate lead optimization, and is most powerful when integrated with information from different sources. Herein is described the use of such methods in conjunction with deconstruction and re-optimization of a diverse series of ASK1 chemotypes along with high-throughput screening that lead to the identification of a novel series of efficient ASK1 inhibitors displaying robust MAP3K pathway inhibition.

PubMed: 28291695
DOI: 10.1016/j.bmcl.2017.02.079

Experimental method

X-RAY DIFFRACTION (2.5 Å)