Laith Q Al-Mawsawi1, Rasha I Al-Safi, Nouri Neamati. 1. University of Southern California, Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Los Angeles, California 90089, USA.
Abstract
BACKGROUND: HIV-1 integrase (IN) represents a therapeutically advantageous viral target to treat HIV/AIDS in the clinic. Over a decade of progress in the field has resulted in IN inhibitor chemical classes that display specificity for strand transfer catalysis of the enzyme, thus blocking viral DNA integration into host cell nuclear DNA, an essential step for viral infectivity. OBJECTIVE: In this manuscript we provide an update on recent HIV-1 IN inhibitors that have been clinically evaluated, which include MK-0518, MK-2048, GS-9137, GS-9160, GS-9224, GSK-364735, and BMS-707035. The information presented here can aid in the IN drug developmental process. METHODS: We have limited the scope of this review to information available on the clinical evaluation of promising strand transfer-specific IN inhibitors and their potential drug-drug interaction profiles with other antiretroviral agents. RESULTS/ CONCLUSION: The development of strand transfer-specific inhibitor classes is an important achievement for the IN drug design and development field. However, continued drug development is needed given that the ability of HIV to replicate under therapeutic pressure will undoubtedly lead to the emergence of IN drug-resistant viral strains.
BACKGROUND: HIV-1 integrase (IN) represents a therapeutically advantageous viral target to treat HIV/AIDS in the clinic. Over a decade of progress in the field has resulted in IN inhibitor chemical classes that display specificity for strand transfer catalysis of the enzyme, thus blocking viral DNA integration into host cell nuclear DNA, an essential step for viral infectivity. OBJECTIVE: In this manuscript we provide an update on recent HIV-1 IN inhibitors that have been clinically evaluated, which include MK-0518, MK-2048, GS-9137, GS-9160, GS-9224, GSK-364735, and BMS-707035. The information presented here can aid in the IN drug developmental process. METHODS: We have limited the scope of this review to information available on the clinical evaluation of promising strand transfer-specific IN inhibitors and their potential drug-drug interaction profiles with other antiretroviral agents. RESULTS/ CONCLUSION: The development of strand transfer-specific inhibitor classes is an important achievement for the IN drug design and development field. However, continued drug development is needed given that the ability of HIV to replicate under therapeutic pressure will undoubtedly lead to the emergence of IN drug-resistant viral strains.
Authors: Manuel Tsiang; Gregg S Jones; Anita Niedziela-Majka; Elaine Kan; Eric B Lansdon; Wayne Huang; Magdeleine Hung; Dharmaraj Samuel; Nikolai Novikov; Yili Xu; Michael Mitchell; Hongyan Guo; Kerim Babaoglu; Xiaohong Liu; Romas Geleziunas; Roman Sakowicz Journal: J Biol Chem Date: 2012-04-25 Impact factor: 5.157
Authors: Horrick Sharma; Shivaputra Patil; Tino W Sanchez; Nouri Neamati; Raymond F Schinazi; John K Buolamwini Journal: Bioorg Med Chem Date: 2011-03-01 Impact factor: 3.641