Disease relevance of Ro5-3335

• The drug Ro 5-3335 [7-chloro-5-(2-pyrryl)-3H-1,4-benzodiazepine-2(H)-one], inhibited gene expression by HIV-1 at the level of transcriptional trans-activation by Tat [1].
• The human immunodeficiency virus type 1 Tat antagonist, Ro 5-3335, predominantly inhibits transcription initiation from the viral promoter [2].
• As a prototype, we have chosen a low-molecular-weight Tat inhibitor, Ro5-3335, and analyzed its effect on HIV-1 replication in the presence of TNF-alpha and HSV-1 infection in acutely infected peripheral blood lymphocytes (PBLs) and T cells [3].

High impact information on Ro5-3335

• Ro 5-3335 [7-chloro-5-(2-pyrryl)-3H-1,4-benzodiazepin-2(H)-one], which inhibits Tat-mediated transactivation of HIV-1, also inhibits the functional interaction between Tat and T3R alpha [4].
• Ro5-3335 was found to inhibit HIV-1 long terminal repeat-driven lacZ gene expression at a 50% inhibitory concentration of 0.5 microM [5].
• The cytotoxicity of Ro5-3335 was significantly lower in peripheral blood lymphocytes than in the CD4+ T-cell lines [5].
• The absence of anti-HIV-1 activity of Ro5-3335 in MT-4 cells was confirmed by using different parameters of virus replication and different multiplicities of infection [5].
• In contrast, Ro5-3335 suppressed TNF-alpha-induced activation of HIV-1 replication in chronically infected T cells and monocytes that both expressed only low levels of HIV-1 constitutively, while its effect in high-expressing OM-10.1 cells was negligible in the presence of TNF-alpha [3].

Chemical compound and disease context of Ro5-3335

• We have examined the activity of the HIV-1 Tat inhibitors Ro-5-3335 and Ro-24-7429 in cultured human peripheral MDMs [6].

Anatomical context of Ro5-3335

• Treatment of chronically HIV-1-infected CD4-negative T cells in vitro with the Tat antagonist Ro 5-3335 resulted in a drug dose-dependent decrease in virus protein production and a reciprocal increase in surface CD4 display [7].
• Here we describe the effects of Ro 5-3335 on the accumulation of viral DNA during primary infection, the induction of virus from a latently infected cell line, and the expression of virus upon activation of naturally infected T cells [8].

Gene context of Ro5-3335

• The induction of HIV-1, as determined by the synthesis of p24 core antigen, was inhibited by 99% by Ro 5-3335 in both the model cell line and naturally infected T cells [8].

References