HIV与艾滋病课件.ppt

* * * * * * * * * * Table 1.Examples of Inhibitors of HIV-1 Cell Entry in Development.* Type of Inhibitor Proposed Mechanism of Action Developmental Status CD4-receptor inhibitors Recombinant soluble CD4 Competitively binds with gp120 receptor Limited activity in phase 1–2 trials TNX-355 Monoclonal antibody against CD4, provides steric hindrance for chemokine receptor binding Phase 1–2 (showing dose-related activity after a single intravenous dose) PRO 542 Tetrameric CD4 incorporated into gamma globulin Phase 1–2 (preliminary evidence of activity after injections) BMS-806 Binds to gp120 to block CD4 binding Preclinical Chemokine-receptor inhibitors SCH-C RANTES antagonist, competitively binds to CCR5 Phase 1–2 (showing short-term activity as oral agent) PRO 140 Monoclonal antibody against CCR5 Preclinical AMD3100 Bicyclam inhibitor of CXCR4 Minimal activity in most patients in phase 2 study of intravenous administration Other attachment inhibitors Dextran sulfate Possible charge-mediated attachment interference, binds gp120 and inhibits CXCR4 interaction Phase 1–2 (showing mixed activity, excessive toxicity) PRO 2000 Binds to CD4 and interferes with gp120 binding Phase 2 in progress, as topical microbicide Cyanovirin-N Binds to gp120, interferes with CD4 and CXCR4 interactions Preclinical, as topical microbicide Membrane-fusion inhibitors Enfuvirtide (T-20) Peptide that interferes with gp41-mediated fusion Phase 3 (showing activity beyond 1 yr from subcuta-neous injections, advantage at 6 mo as part of salvage regimen); FDA approved for clinical use T-1249 Peptide that interferes with gp41-mediated fusion Phase 1–2 (showing short-term activity from subcu-taneous injections, proof of concept to support use as salvage treatment for patients with enfu-virtide-resistant virus) “Five-helix” Binds to C terminal of gp41 to form stable six-helix structure, inhibits fusion Preclinical * 阿昔洛韦（acyclov