Small-molecule CCR5 inhibitors

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],... 

Kuhmann, S.E. et al. (2004) Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor. JoumaJ of Virology, 78 (6), 2790-2807. 

J., Palani, A., Shapiro, S., Clader, J. W., McCombie, S., Reyes, G. R., Baroudy, B. M., and Moore, J. P. (2002). HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc. Natl. Acad. Sci. USA 99 395-100. 

Small Molecule CCR5 and CXCR4-Based Viral Entry Inhibitors for Anti-HIV Therapy Currently in Development Wieslaw M. Kazmierski, Kristjan S. Gudmundsson and Stephen C. Piscitelli ... 

Small Molecule CCR5 and CXCR4-Based Viral Entry Inhibitors... 

Kazmierski W, Bifulco N, Yang H, et al. Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors. Bioorganic Medicinal Chem 2003 11 2663-76. 

Dorr P, Westby M, Dobbs S, et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Anti-microb Agents Chemother 2005 49(l 1 ) 4721 —4732. 

Dragic, T., Trkola, A., Thompson, D.A., Cormier, E.G., Kajumo, F.A., Maxwell, E., Lin, S.W., Ying, W., Smith, S.O., Sakmar, T.P., and Moore, J.P. (2000) A binding pocket for a small molecule inhibitor of HlV-1 entry within the transmembrane helices of CCR5. Proceedings ofthe National Academy of Sciences of the United States if America, 97, 5639-5644. 

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