2-Glycineamide-5-chlorophenyl 2-pyrryl ketone, a non-benzodiazepin Tat antagonist, is effective against acute and chronic HIV-1 infections in vitro.

ABSTRACT

In the search for effective Tat-dependent transcription inhibitors using a screening assay system that has recently been developed, 2-glycineamide-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 replication in both acutely and chronically infected cells. The 50% effective concentration (EC50) of GCPK in acutely infected MOLT-4 and CEM cells was 0.62 and 0.13 microgram/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 replication in MOLT-4/IIIB (MOLT-4 cells chronically infected with HIV-1) and tumor necrosis factor-alpha-(TNF-alpha)-induced viral activation in OM10.1 cells (a HL-60 clone latently infected with HIV-1). GCPK is distinct from Ro5-3335 and Ro24-7429 in that this novel Tat-dependent transcription inhibitor has no benzodiazepin ring.