molecules of the month

Newly disclosed HIV-1 antiretroviral is the first integrase-LEDGF/p75 allosteric HIV-1 inhibitor to clear Ph. I safety trials. Biodim has recently disclosed a small molecule candidate, BDM-2, that demonstrates nanomolar activity against HIV-1 replication in vitro and showed promising safety in healthy subjects in a 2020 Ph. I clinical trial (NCT03634085). BDM-2 is an allosteric HIV-1 integrase (IN) inhibitor (ALLINI), a class of compounds discovered prior to 2009 by Boehringer Ingelheim (WO2009/062285A1) that have a distinct mechanism of action from other HIV antiretroviral therapies, potentially offering a route to countering HIV mutants that are resistant to existing therapies. The molecule is highly potent, with an EC50 of 8.7 nM  for HIV-1 NL4-3 inhibition in MT4 cells (via HTFR), exceeding that of…