Chemotherapy of the acquired immune deficiency syndrome (AIDS): non-nucleoside inhibitors of the human immunodeficiency virus type 1 reverse transcriptase.

Abstract:

Several classes of non-nucleotide analogues (i.e. TIBO and HEPT derivatives) have been identified that specifically interact with the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1). These derivatives inhibit the replication of HIV-1 in various cell lines, including peripheral blood lymphocytes and monocytes/macrophages, at concentrations that are 10,000- to 100,000-fold lower than the cytotoxic concentrations. At the HIV-1 RT level, they appear to interact with a specific allosteric "TIBO" site, which may be functionally and also structurally associated with the substrate binding site. The TIBO and TIBO-like compounds are orally bioavailable. In vivo they sustain plasma drug levels that are well above the concentrations required to inhibit virus replication in vitro.

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