An internal standard for the quantification of maraviroc
Maraviroc-d6 is intended for use as an internal standard for the quantification of maraviroc . Maraviroc is an antagonist of the chemokine (C-C motif) receptor 5 (CCR5; Ki = 0.24 nM for the rhesus monkey recombinant receptor).1 It inhibits binding of chemokine (C-C motif) ligand 3 (CCL3), CCL4, and CCL5 to HEK293 cell membranes expressing CCR5 (IC50s = 3.3, 7.2, and 5.2 nM, respectively) and inhibits HIV-1 binding to CCR5 via glycoprotein 120 (gp120) and gp160 (IC50s = 11 and 0.22 nM, respectively).2 Maraviroc is selective for CCR5 over CCR1, -2, -3, -4, -7, and -8, and CXCR1 and -2 in a panel of immunological assays for ligand-induced cell chemotaxis and ligand-receptor binding (IC50s = >10 μM for all). It has antiviral activity against laboratory and clinical isolates of CCR5-tropic (IC50s = 0.1-1.1 nM), but not CXCR4-tropic or dual tropic (IC50s = >10 μM for all), HIV-1 in isolated human peripheral blood mononuclear cells (PBMCs). Maraviroc prevents infection upon exposure to HIV-1 in humanized RAG-hum mice when administered at a dose of 62 mg/kg.3
|1. Yuan, Y., Arnatt, C.K., El-Hage, N., et al. A bivalent ligand targeting the putative mu opioid receptor and chemokine receptor CCR5 heterodimers: binding affinity versus functional activities. Medchemcomm. 4(5), 847-851 (2013).|2. 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. Antimicrob. Agents Chemother. 49(11), 4721-4732 (2005).|3. Neff, C.P., Ndolo, T., Tandon, A., et al. Oral pre-exposure prophylaxis by anti-retrovirals raltegravir and maraviroc protects against HIV-1 vaginal transmission in a humanized mouse model. PLoS One 5(12), e15257 (2010).
动态评分
0.0