5IVT

Crystal Structure of HIV Protease complexed with [(1S)-1-[(S)-(4-chlorophenyl)-(3,5-difluorophenyl)methyl]-2-[[5-fluoro-4-[2-[(2R,5S)-5-(2,2,2-trifluoroethylcarbamoyloxymethyl)morpholin-4-ium-2-yl]ethyl]pyridin-1-ium-3-yl]amino]-2-oxo-ethyl]ammonium

Summary for 5IVT

• Entry DOI: 10.2210/pdb5ivt/pdb
• Related: 5IVQ 5IVR 5IVS
• Descriptor: Protease, ACETATE ION, (betaS)-4-chloro-beta-(3,5-difluorophenyl)-N-(5-fluoro-4-{2-[(2R,5S)-5-({[(2,2,2-trifluoroethyl)carbamoyl]oxy}methyl)morpholin-2-yl]ethyl}pyridin-3-yl)-L-phenylalaninamide, ... (5 entities in total)
• Functional Keywords: hiv, protease, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 2
• Total formula weight: 23146.68

Authors

Su, H.P. (deposition date: 2016-03-21, release date: 2016-05-18, Last modification date: 2024-03-06)

Primary citation

Bungard, C.J.,Williams, P.D.,Ballard, J.E.,Bennett, D.J.,Beaulieu, C.,Bahnck-Teets, C.,Carroll, S.S.,Chang, R.K.,Dubost, D.C.,Fay, J.F.,Diamond, T.L.,Greshock, T.J.,Hao, L.,Holloway, M.K.,Felock, P.J.,Gesell, J.J.,Su, H.P.,Manikowski, J.J.,McKay, D.J.,Miller, M.,Min, X.,Molinaro, C.,Moradei, O.M.,Nantermet, P.G.,Nadeau, C.,Sanchez, R.I.,Satyanarayana, T.,Shipe, W.D.,Singh, S.K.,Truong, V.L.,Vijayasaradhi, S.,Wiscount, C.M.,Vacca, J.P.,Crane, S.N.,McCauley, J.A.
Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group.
Acs Med.Chem.Lett., 7:702-707, 2016

PubMed Abstract: A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.

PubMed: 27437081
DOI: 10.1021/acsmedchemlett.6b00135

Experimental method

X-RAY DIFFRACTION (1.15 Å)