Research progress on chemokine receptor 5-targeted therapy for HIV-1 / 病毒学报

Along with the spread of human immunodeficiency virus 1 (HIV-1) infection in the world and the emergence of drug-resistant viral strains, it is urgent to seek the novel potent therapies. Chemokine receptor 5 (CCR5) is one of the main coreceptors involved in the entry of HIV-1 into target cells. Nowadays, a number of CCR5 antagonists have been developed and some of them have progressed to clinical trials or been approved. Research progress has also been made in the CCR5-targeted gene therapy. This review summarizes the recent research progress on the CCR5-targeted drug and gene therapy.

DT-13, a saponin of dwarf lilyturf tuber, exhibits anti-cancer activity by down-regulating C-C chemokine receptor type 5 and vascular endothelial growth factor in MDA-MB-435 cells / 中国天然药物

AIM@#To investigate the anticancer activity of DT-13 under normoxia and determine the underlying mechanisms of action.@*METHODS@#MDA-MB-435 cell proliferation, migration, and adhesion were performed to assess the anticancer activity of DT-13, a saponin from Ophiopogon japonicus, in vitro. In addition, the effects of DT-13 on tumor growth and metastasis in vivo were evaluated by orthotopic implantation of MDA-MB-435 cells into nude mice; mRNA levels of vascular endothelial growth factor (VEGF), C-C chemokine receptor type 5 (CCR5) and hypoxia-inducible factor 1α (HIF-1α) were evaluated by real-time quantitative PCR; and CCR5 protein levels were detected by Western blot assay.@*RESULTS@#At 0.01 to 1 μmol·L(-1), DT-13 inhibited MDA-MB-435 cell proliferation, migration, and adhesion significantly in vitro. DT-13 reduced VEGF and CCR5 mRNAs, and decreased CCR5 protein expression by down-regulating HIF-1α. In addition, DT-13 inhibited MDA-MB-435 cell lung metastasis, and restricted tumor growth slightly in vivo.@*CONCLUSION@#DT-13 inhibited MDA-MB-435 cell proliferation, adhesion, and migration in vitro, and lung metastasis in vivo by reducing VEGF, CCR5, and HIF-1α expression.

Acute toxicity of CCR5 antagonist C25P polypeptide in mice and its carcinogenicity in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the acute toxicity of C25P polypeptide, a CCR5 antagonist, in mice and its carcinogenic effect in vitro.</p><p><b>METHODS</b>The acute toxicity of C25P polypeptide in mice was assessed by determining the maximum tolerated dose (MTD). The mice were given C25P at the dose of 3.64 g/kg by tail vein injection, and the control mice received saline (40 ml/kg) injection. The mice were continuously observed for 14 days after the administration and sacrificed on day 14 for routine blood test, examination of the blood biochemistry and pathological examination. The carcinogenicity of C25P polypeptide in vitro was evaluated in cultured cell lines by chromosome aberration test, cell transformation test and non-anchorage dependent growth test.</p><p><b>RESULTS</b>No mice died following administration of the drug, but 3 mice showed mild adverse reactions. The rats in both groups showed an increase in the body weight at a comparable rate. GPT increased and ALP decreased significantly in C25P polypeptide group (P<0.05). Most of the organs of the rats treated with in C25P polypeptide remained normal, but 3 mice showed pathologies in the lung, spleen and liver. Chromosome aberration test, cell transformation test and non-anchorage-dependent growth test all yielded negative results for C25P polypeptide.</p><p><b>CONCLUSION</b>C25P polypeptide is a low-toxicity drug that produces no apparent acute toxicity in mice or obvious carcinogenicity in vitro.</p>

HIV entry inhibitors: progress in development and application / 药学学报

This review discusses recent progress in the development of anti-HIV agents, with emphasis on small molecule HIV-1 entry inhibitors. The entry inhibitors primarily target HIV-1 envelope glycoproteins or the cellular receptors, CD4 and chemokine receptors. Two of the entry inhibitors, enfuvirtide and maraviroc, have been approved by the US FDA for AIDS therapy. The drug resistance associated with some of the entry inhibitors will also be discussed.

CCR5, a new target of anti-HIV drugs / 中国医学科学院学报

CCR5, a membrane protein on cell surface, is a member of the G protein-coupled receptor superfamily and one of the major co-receptors for HIV-1 infection. The roles of CCR5 in HIV-1 infection have been elucidated since 1996. Because of the biological nature of CCR5, it has became a molecular target for the novel drugs against HIV-1. Antagonists for CCR5 could be grouped as following, chemokine derivatives, small molecule non-peptide compounds, monoclonal antibodies and peptides. The latest progress in this field is reviewed in this article.