The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic

Vigneshwaran Namasivayam, Murugesan Vanangamudi, Victor G. Kramer, Sonali Kurup, Peng Zhan, Xinyong Liu, Jacob Kongsted, Siddappa Nagadenahalli Byrareddy

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4851-4883
Number of pages33
JournalJournal of Medicinal Chemistry
Volume62
Issue number10
DOIs
StatePublished - May 23 2019

Fingerprint

Reverse Transcriptase Inhibitors
HIV-1
Rilpivirine
efavirenz
etravirine
HIV
Delavirdine
Nevirapine
Pandemics
Virus Diseases
Antiviral Agents
Mutation
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic. / Namasivayam, Vigneshwaran; Vanangamudi, Murugesan; Kramer, Victor G.; Kurup, Sonali; Zhan, Peng; Liu, Xinyong; Kongsted, Jacob; Byrareddy, Siddappa Nagadenahalli.

In: Journal of Medicinal Chemistry, Vol. 62, No. 10, 23.05.2019, p. 4851-4883.

Research output: Contribution to journalReview article

Namasivayam, V, Vanangamudi, M, Kramer, VG, Kurup, S, Zhan, P, Liu, X, Kongsted, J & Byrareddy, SN 2019, 'The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic', Journal of Medicinal Chemistry, vol. 62, no. 10, pp. 4851-4883. https://doi.org/10.1021/acs.jmedchem.8b00843
Namasivayam, Vigneshwaran ; Vanangamudi, Murugesan ; Kramer, Victor G. ; Kurup, Sonali ; Zhan, Peng ; Liu, Xinyong ; Kongsted, Jacob ; Byrareddy, Siddappa Nagadenahalli. / The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic. In: Journal of Medicinal Chemistry. 2019 ; Vol. 62, No. 10. pp. 4851-4883.
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