Discovery of Bioavailable 4,4-Disubstituted Piperidines as Potent Ligands of the Chemokine Receptor 5 and Inhibitors of the Human Immunodeficiency Virus-1

2008 ◽  
Vol 51 (20) ◽  
pp. 6538-6546 ◽  
Author(s):  
Wieslaw M. Kazmierski ◽  
Christopher Aquino ◽  
Brian A. Chauder ◽  
Felix Deanda ◽  
Robert Ferris ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Chemokine Receptor ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus 1 ◽  
Chemokine Receptor 5

Chemokine and Chemokine Receptor Gene Variants and Risk of Non-Hodgkin’s Lymphoma in Human Immunodeficiency Virus-1–Infected Individuals

Blood ◽  
1999 ◽  
Vol 93 (6) ◽  
pp. 1838-1842 ◽  
Author(s):  
Charles S. Rabkin ◽  
Quan-en Yang ◽  
James J. Goedert ◽  
Giao Nguyen ◽  
Hiroaki Mitsuya ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Chemokine Receptor ◽  
Receptor Gene ◽  
Hodgkin's Lymphoma ◽  
Gene Variants ◽  
Non Hodgkin's Lymphoma ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1 ◽  
Chemokine Receptor Gene

Normal B-lymphocyte maturation and proliferation are regulated by chemotactic cytokines (chemokines), and genetic polymorphisms in chemokines and chemokine receptors modify progression of human immunodeficiency virus-1 (HIV-1) infection. Therefore, 746 HIV-1–infected persons were examined for associations of previously described stromal cell-derived factor 1 (SDF-1) chemokine and CCR5 and CCR2 chemokine receptor gene variants with the risk of B-cell non-Hodgkin’s lymphoma (NHL). The SDF1-3′A chemokine variant, which is carried by 37% of whites and 11% of blacks, was associated with approximate doubling of the NHL risk in heterozygotes and roughly a fourfold increase in homozygotes. After a median follow-up of 11.7 years, NHL developed in 6 (19%) of 30 SDF1-3′A/3′A homozygotes and 22 (10%) of 202 SDF1-+/3′A heterozygotes, compared with 24 (5%) of 514 wild-type subjects. The acquired immunodeficiency syndrome (AIDS)-protective chemokine receptor variant CCR5-▵32 was highly protective against NHL, whereas the AIDS-protective variant CCR2-64I had no significant effect. Racial differences in SDF1-3′A frequency may contribute to the lower risk of HIV-1–associated NHL in blacks compared with whites. SDF-1 genotyping of HIV-1–infected patients may identify subgroups warranting enhanced monitoring and targeted interventions to reduce the risk of NHL.

Obstacles and options in the quest for drug candidates against vascular disease

2010 ◽  
Vol 104 (07) ◽  
pp. 1-3 ◽  
Author(s):  
Christian Weber
Keyword(s):  
Metabolic Disease ◽  
Human Immunodeficiency Virus ◽  
Clinical Trials ◽  
Chemokine Receptor ◽  
Drug Candidates ◽  
Immunodeficiency Virus ◽  
Aging Populations ◽  
Ccr5 Antagonists ◽  
Cc Chemokine Receptor 5 ◽  
Human Immunodeficiency Virus 1

Summaryhe difficulties in cardiovascular drug development have been exposed by recent clinical trials, which have uncovered various limitations of promising drug candidates. Yet, the imperative to improve medical treatment of atherosclerosis in aging populations afflicted by metabolic disease remains unbroken. Herein alternatives to metabolically active compounds such as glitazones and torcetrapib are introduced and discussed, namely CC chemokine receptor 5 (CCR5) antagonists recently approved for treatment of patients with human immunodeficiency virus-1, interceptors of proatherogenic chemokine interactions, and actively protective pathways. A combination of different strategies may yield improved safety profiles of these therapeutics.

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