2-GLYCINEAMIDE-5-CHLOROPHENYL 2-PYRRYL KETONE, A NON-BENZODIAZEPIN TAT ANTAGONIST, IS EFFECTIVE AGAINST ACUTE AND CHRONIC HIV-1 INFECTIONS IN-VITRO

In the search for effective Tat-dependent transcription inhibitors usi ng a screening assay system that has recently been developed, 2-glycin eamide-5-chlorophenyl 2-pyrryl ketone (GCPK) has proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1 ) replication in vitro. This compound was inhibitory to HIV-1 replicat ion in both acutely and chronically infected cells. The 50% effective concentration (EC,,) of GCPK in acutely infected MOLT-4 and CEM cells was 0.62 and 0.13 mu g/ml, respectively. These values were similar to those of the known Tat-dependent transcription inhibitors Ro5-3335 and Ro24-7429. Like these inhibitors, GCPK could inhibit HIV-1 replicatio n in MOLT-4/IIIB (MOLT-4 cells chronically infected with HIV-1) and tu mor necrosis factor-alpha- (TNF-alpha)-induced viral activation in OM1 0.1 cells (a HL-60 clone latently infected with HIV-1). GCPK is distin ct from Ro5-3335 and Ro24-7429 in that this novel Tat-dependent transc ription inhibitor has no benzodiazepin ring.