1OHR

VIRACEPT (R) (NELFINAVIR MESYLATE, AG1343): A POTENT ORALLY BIOAVAILABLE INHIBITOR OF HIV-1 PROTEASE

Summary for 1OHR

• Entry DOI: 10.2210/pdb1ohr/pdb
• Descriptor: ASPARTYLPROTEASE, 2-[2-HYDROXY-3-(3-HYDROXY-2-METHYL-BENZOYLAMINO)-4-PHENYL SULFANYL-BUTYL]-DECAHYDRO-ISOQUINOLINE-3-CARBOXYLIC ACID TERT-BUTYLAMIDE (3 entities in total)
• Functional Keywords: aspartyl protease, hydrolase, hiv-i protease
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 2
• Total formula weight: 22175.29

Authors

Davies II, J.F. (deposition date: 1997-09-27, release date: 1998-12-09, Last modification date: 2024-02-14)

Primary citation

Kaldor, S.W.,Kalish, V.J.,Davies 2nd., J.F.,Shetty, B.V.,Fritz, J.E.,Appelt, K.,Burgess, J.A.,Campanale, K.M.,Chirgadze, N.Y.,Clawson, D.K.,Dressman, B.A.,Hatch, S.D.,Khalil, D.A.,Kosa, M.B.,Lubbehusen, P.P.,Muesing, M.A.,Patick, A.K.,Reich, S.H.,Su, K.S.,Tatlock, J.H.
Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease.
J.Med.Chem., 40:3979-3985, 1997

PubMed Abstract: Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively. In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans. AG1343 (Viracept) has recently been approved for marketing for the treatment of AIDS.

PubMed: 9397180
DOI: 10.1021/jm9704098

Experimental method

X-RAY DIFFRACTION (2.1 Å)