4WVS

Crystal structure of XIAP-BIR2 domain complexed with (S)-3-(4-methoxyphenyl)-2-((S)-2-((S)-1-((S)-2-((S)-2-(methylamino)propanamido)pent-4-ynoyl)pyrrolidine-2-carboxamido)-3-phenylpropanamido)propanoic acid

Summary for 4WVS

• Entry DOI: 10.2210/pdb4wvs/pdb
• Related: 4WVT 4WVU
• Descriptor: E3 ubiquitin-protein ligase XIAP, 3,11-DIFLUORO-6,8,13-TRIMETHYL-8H-QUINO[4,3,2-KL]ACRIDIN-13-IUM, ZINC ION, ... (6 entities in total)
• Functional Keywords: iap, xiap-bir2, apoptosis
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: P98170
• Total number of polymer chains: 2
• Total formula weight: 12481.10

Authors

Pokross, M.E. (deposition date: 2014-11-07, release date: 2015-05-06, Last modification date: 2023-11-15)

Primary citation

Seigal, B.A.,Connors, W.H.,Fraley, A.,Borzilleri, R.M.,Carter, P.H.,Emanuel, S.L.,Fargnoli, J.,Kim, K.,Lei, M.,Naglich, J.G.,Pokross, M.E.,Posy, S.L.,Shen, H.,Surti, N.,Talbott, R.,Zhang, Y.,Terrett, N.K.
The Discovery of Macrocyclic XIAP Antagonists from a DNA-Programmed Chemistry Library, and Their Optimization To Give Lead Compounds with in Vivo Antitumor Activity.
J.Med.Chem., 58:2855-2861, 2015

PubMed Abstract: Affinity selection screening of macrocycle libraries derived from DNA-programmed chemistry identified XIAP BIR2 and BIR3 domain inhibitors that displace bound pro-apoptotic caspases. X-ray cocrystal structures of key compounds with XIAP BIR2 suggested potency-enhancing structural modifications. Optimization of dimeric macrocycles with similar affinity for both domains were potent pro-apoptotic agents in cancer cell lines and efficacious in shrinking tumors in a mouse xenograft model.

PubMed: 25695766
DOI: 10.1021/jm501892g

Experimental method

X-RAY DIFFRACTION (2.09 Å)