Fragment based strategies for discovery of novel HIV-1 reverse transcriptase and integrase inhibitors

Catherine F. Latham, Jennifer La, Ricky N. Tinetti, David K. Chalmers, Gilda Tachedjian

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

Human immunodeficiency virus (HIV) remains a global health problem. While combined antiretroviral therapy has been successful in controlling the virus in patients, HIV can develop resistance to drugs used for treatment, rendering available drugs less effective and limiting treatment options. Initiatives to find novel drugs for HIV treatment are ongoing, although traditional drug design approaches often focus on known binding sites for inhibition of established drug targets like reverse transcriptase and integrase. These approaches tend towards generating more inhibitors in the same drug classes already used in the clinic. Lack of diversity in antiretroviral drug classes can result in limited treatment options, as cross-resistance can emerge to a whole drug class in patients treated with only one drug from that class. A fresh approach in the search for new HIV-1 drugs is fragment-based drug discovery (FBDD), a validated strategy for drug discovery based on using smaller libraries of low molecular weight molecules (
Original languageEnglish
Pages (from-to)1135-1153
Number of pages19
JournalCurrent Topics in Medicinal Chemistry
Volume16
Issue number10
DOIs
Publication statusPublished - 2016

Keywords

  • Antiretrovirals
  • Fragment screening
  • Fragment-based drug discovery
  • HIV-1
  • Integrase
  • Reverse transcriptase

Cite this

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abstract = "Human immunodeficiency virus (HIV) remains a global health problem. While combined antiretroviral therapy has been successful in controlling the virus in patients, HIV can develop resistance to drugs used for treatment, rendering available drugs less effective and limiting treatment options. Initiatives to find novel drugs for HIV treatment are ongoing, although traditional drug design approaches often focus on known binding sites for inhibition of established drug targets like reverse transcriptase and integrase. These approaches tend towards generating more inhibitors in the same drug classes already used in the clinic. Lack of diversity in antiretroviral drug classes can result in limited treatment options, as cross-resistance can emerge to a whole drug class in patients treated with only one drug from that class. A fresh approach in the search for new HIV-1 drugs is fragment-based drug discovery (FBDD), a validated strategy for drug discovery based on using smaller libraries of low molecular weight molecules (",
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Fragment based strategies for discovery of novel HIV-1 reverse transcriptase and integrase inhibitors. / Latham, Catherine F.; La, Jennifer; Tinetti, Ricky N.; Chalmers, David K.; Tachedjian, Gilda.

In: Current Topics in Medicinal Chemistry, Vol. 16, No. 10, 2016, p. 1135-1153.

Research output: Contribution to journalArticleResearchpeer-review

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