HIV/AIDS is a devastating disease with no cure. Current treatment regimens are strict and overwhelming but very effective in controlling the severity and morbidity of the disease. However, long-term use has begun to uncover significant side effects. A new class of drugs called HIV entry inhibitors has been envisioned that will be a significant addition to the arsenal. Blocking of the CCR5 or CXCR4 coreceptors will prevent the entry of the virus into the macrophages or T cells, respectively. Library screening and peptide analoging will continue, making use of our expressed, solubilized, immobilized receptors and affinity purified ligands from these libraries, to increase potency and specificity and develop a lead compound to inhibit HIV infection. Full characterization of the inhibitors will be performed to determine the mechanism of action and the efficacy of the compound. Toxicity and pharmacokinetic studies will be performed on the lead compound after scale-up and formulation to enable an IND filing. Although initial preclinical and clinical studies will be performed with a subcutaneous injectable formulation, the goal of this research is to develop a controlled-release injectable depot formulation of a CCR5 inhibitor. PROPOSED COMMERCAIL APPLICATION: NOT AVAILABLE
