Current Topics in Medicinal Chemistry

Author(s): Christophe Marchand, Kasthuraiah Maddali, Mathieu Metifiot and Yves Pommier

DOI: 10.2174/156802609789630910

HIV-1 IN Inhibitors: 2010 Update and Perspectives

Page: [1016 - 1037] Pages: 22

  • * (Excluding Mailing and Handling)

Abstract

Integrase (IN) is the newest validated target against AIDS and retroviral infections. The remarkable activity of raltegravir (Isentress®) led to its rapid approval by the FDA in 2007 as the first IN inhibitor. Several other IN strand transfer inhibitors (STIs) are in development with the primary goal to overcome resistance due to the rapid occurrence of IN mutations in raltegravir-treated patients. Thus, many scientists and drug companies are actively pursuing clinically useful IN inhibitors. The objective of this review is to provide an update on the IN inhibitors reported in the last two years, including second generation STI, recently developed hydroxylated aromatics, natural products, peptide, antibody and oligonucleotide inhibitors. Additionally, the targeting of IN cofactors such as LEDGF and Vpr will be discussed as novel strategies for the treatment of AIDS.

Keywords: HIV-1 IN, diketo acids, HIV inhibitors, AIDS, IN inhibitors, peptides, oligonucleotides