CCR5 inhibitor

Pugach P, Marozsan AJ, Ketas TJ, Landes EL, Moore JP, Kuhmann SE (2007) HIV-1 clones resistant to a small molecule CCR5 inhibitor use the inhibitor-bound form of CCR5 for entry. Virology 361 212-228... 

Marozsan AJ, Kuhmann SE, Morgan T, et al. Generation and properties of a human immunodeficiency virus type 1 isolate resistant to the small molecule CCR5 inhibitor, SCH-417690 (SCH-D). Virology 2005 338(1) 182-199. 

TAK-652 (Figure 4) is yet another small-molecule CCR5 inhibitor currently in the clinic. Published data suggest that TAK-652 potently inhibits the macrophage-tropic HIV-1 clinical isolates in peripheral blood mononuclear cells with the mean IC90 = 0.25 nM [28],... 

Figure 8 Other selected CCR5 inhibitors from patent and peer-reviewed literature. 

Scheme 18 Solid phase synthesis of spirodiketopiperazme CCR5 inhibitors with two representative 3D conformations of 114A (blue) and 114B (cyan). Yield shown represents yield over all steps...

Maraviroc CCR5 inhibitor 300 mg bid Muscle and joint pain, diarrhea, sleep disturbance, + liver enzymes See footnote 4 for medications that must be -administered with caution. Decrease dose to 150 mg bid with CYP3A inhibitors and increase to 600 mg bid with CYP3A inducers. Avoid rifampin... 

Maeda, K. et al. Structural and molecular interactions of CCR5 inhibitors with CCR5. J. Biol. Chem. 2006, 281, 12688-12698. 

Muirhead G, Abel S, Russell D, Hackman F, Taylor-Worth R, TohM, TanLH. An investi -tion of the effects of atazanavir and ritonavir boosted atazanavir onthephanncokineticsofthe novel CCR5 inhibitor UK-427,857. 7 International Congress on Drug Ther y in HIV infection, Glasgow, UK, 14-18 November 2004. 

NedeUec, R., Coetzer, M., Lederman, M. M., Offord, R. E., Hartley, O., Mosier, D. E. (2011). Resistance to the CCR5 inhibitor 5P12-ITANTES requires a difficult evolution from CCR5 to CXCR4 coreceptor use. PLoS One, 6, e22020. 

Maeda, K., Nakata, H., Koh, Y., Miyakawa, T., Ogata, H., Takaoka, Y., et al. (2004). Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/ CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro. Journal of Virology, 7S(16), 8654-8662. http //dx.doi.org/10.1128/ JVI.78.16.8654-8662.2004. 

Dorr, P and Perros, M. (2008) CCR5 inhibitors in HIV-1 therapy. Expert Opinion on Drug Discovery, 3 (11), 1345-1361. 

Wilkin, T. et al. (2008) The relationship of CCR5 inhibitors to CD4 count changes a meta-analysis of recent clinical trials in treatment-experienced subjects (abstract 800). 15th Conference on Retrovimses and Opportunistic Infections. 2008 Boston, USA. 

Maeda, K. et al. (2004) Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro. Journal of Virology, 78 (16), 8654—8662. 

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