TY - JOUR
T1 - The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic
AU - Namasivayam, Vigneshwaran
AU - Vanangamudi, Murugesan
AU - Kramer, Victor G.
AU - Kurup, Sonali
AU - Zhan, Peng
AU - Liu, Xinyong
AU - Kongsted, Jacob
AU - Byrareddy, Siddappa N.
N1 - Funding Information:
V.M acknowledges SERB-DST (Science & Engineering Research Board, Government of India) for a Young Scientist Awards (YSS/2015/001938). S.N.B. thanks NIH R01-AI129745 and MH062261 for financial support. Z.P. acknowledges the Young Scholars Program of Shandong University (YSPSDU no. 2016WLJH32) and the Fundamental Research Funds of Shandong University (no. 2017JC006). L.X. thanks the Key Project of NSFC for International Cooperation (no. 81420108027) and the Key Research and Development Project of Shandong Province (no. 2017CXGC1401). We thank the European Molecular Biology Laboratory (EMBL) for providing the evaluation license of LigPlot+. We are indebted to Dr. Vasanthanathan Poongavanam for his valuable discussion during the design of this manuscript and preparation of figures, and we are also thankful to Dr. Mohit Tyagi, Uppsala University, Sweden, for his rigorous proofreading of synthetic schemes for the manuscript.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2019/5/23
Y1 - 2019/5/23
N2 - Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a definitive place due to their unique antiviral potency, high specificity, and low toxicity in antiretroviral combination therapies used to treat HIV. Until now, >50 structurally diverse classes of compounds have been reported as NNRTIs. Among them, six NNRTIs were approved for HIV-1 treatment, namely, nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETR), rilpivirine (RPV), and doravirine (DOR). In this perspective, we focus on the six NNRTIs and lessons learned from their journey through development to clinical studies. It demonstrates the obligatory need of understanding the physicochemical and biological principles (lead optimization), resistance mutations, synthesis, and clinical requirements for drugs.
AB - Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a definitive place due to their unique antiviral potency, high specificity, and low toxicity in antiretroviral combination therapies used to treat HIV. Until now, >50 structurally diverse classes of compounds have been reported as NNRTIs. Among them, six NNRTIs were approved for HIV-1 treatment, namely, nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETR), rilpivirine (RPV), and doravirine (DOR). In this perspective, we focus on the six NNRTIs and lessons learned from their journey through development to clinical studies. It demonstrates the obligatory need of understanding the physicochemical and biological principles (lead optimization), resistance mutations, synthesis, and clinical requirements for drugs.
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U2 - 10.1021/acs.jmedchem.8b00843
DO - 10.1021/acs.jmedchem.8b00843
M3 - Review article
C2 - 30516990
AN - SCOPUS:85059650953
VL - 62
SP - 4851
EP - 4883
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 10
ER -