Hsu M C, Schutt A D, Holly M, Slice L W, Sherman M I, Richman D D, Potash M J, Volsky D J
Department of Virology, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Biochem Soc Trans. 1992 May;20(2):525-31. doi: 10.1042/bst0200525.
Ro 5-3335, 7-chloro-5-(2-pyrryl)-3H-1,4-benzo-diazepin-2-(H)-one, has been shown to inhibit gene expression controlled by the human immunodeficiency virus-1 (HIV-1) LTR promoter. The inhibition was specific for the viral transcriptional transactivator Tat. The compound did not inhibit the basal activity of the HIV-1 LTR or the activity of promoters not responsive to Tat. Consistent with its mode of action, Ro 5-3335 inhibited HIV-1 replication (IC50 = 0.1-1 microM) by reducing viral RNA synthesis in acutely, as well as chronically, infected cells in vitro. The compound was active against HIV-1 and HIV-2, and AZT-resistant clinical isolates.
Ro 5-3335，即7-氯-5-（2-吡咯基）-3H-1,4-苯并二氮杂卓-2-酮，已被证明可抑制由人类免疫缺陷病毒1型（HIV-1）长末端重复序列（LTR）启动子控制的基因表达。这种抑制作用对病毒转录反式激活因子Tat具有特异性。该化合物不抑制HIV-1 LTR的基础活性，也不抑制对Tat无反应的启动子的活性。与其作用方式一致，Ro 5-3335通过减少急性和慢性感染细胞中的病毒RNA合成来抑制HIV-1复制（IC50 = 0.1 - 1 microM）。该化合物对HIV-1、HIV-2以及耐齐多夫定的临床分离株均有活性。
