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 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.
Department of Microbiology, Fukushima Medical College, Japan.
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Hashimoto
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Baba
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Okamoto
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Shigeta
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002460:Cell Line; D015696:Gene Products, tat / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015394:Molecular Structure; D011758:Pyrroles / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
C103626:2-glycineamide-5-chlorophenyl-2-pyrryl ketone; D019380:Anti-HIV Agents; D001570:Benzodiazepinones; D015696:Gene Products, tat; D011758:Pyrroles; D054322:tat Gene Products, Human Immunodeficiency Virus; D001569:Benzodiazepines; C070024:Ro 24-7429; C072173:Ro 5-3335