Genomes and Genes
Summary: Six-carbon alicyclic hydrocarbons.
- Ratcliff A, Shi W, Arts E. HIV-1 resistance to maraviroc conferred by a CD4 binding site mutation in the envelope glycoprotein gp120. J Virol. 2013;87:923-34 pubmed publisher..In contrast, our structural models on K425 gp120 suggest that this resistant mutation impacts CD4 interactions and highlights a novel pathway for MVC resistance...
- Rossi R, Lichtner M, De Rosa A, Sauzullo I, Mengoni F, Massetti A, et al. In vitro effect of anti-human immunodeficiency virus CCR5 antagonist maraviroc on chemotactic activity of monocytes, macrophages and dendritic cells. Clin Exp Immunol. 2011;166:184-90 pubmed publisher..The drug might have a potential role in the down-regulation of HIV-associated chronic inflammation by blocking the recirculation and trafficking of MO and MDC. ..
- Lin H, Chooi Y, Dhingra S, Xu W, Calvo A, Tang Y. The fumagillin biosynthetic gene cluster in Aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of ?-trans-bergamotene. J Am Chem Soc. 2013;135:4616-9 pubmed publisher..More significantly, we uncovered the elusive ?-trans-bergamotene synthase in A. fumigatus as a membrane-bound terpene cyclase...
- Zou Y, Li J, Ma H, Jiang H, Yuan J, Gong H, et al. Heat shock transcription factor 1 protects heart after pressure overload through promoting myocardial angiogenesis in male mice. J Mol Cell Cardiol. 2011;51:821-9 pubmed publisher..We conclude that HSF1 promotes cardiac angiogenesis through suppression of p53 and subsequent upregulation of HIF-1 in endothelial cells during chronic pressure overload, leading to the maintenance of cardiac adaptation. ..
- Gutierrez C, Diaz L, Vallejo A, Hernandez Novoa B, Abad M, Madrid N, et al. Intensification of antiretroviral therapy with a CCR5 antagonist in patients with chronic HIV-1 infection: effect on T cells latently infected. PLoS ONE. 2011;6:e27864 pubmed publisher..No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results. ClinicalTrials.gov NCT00795444. ..
- Swenson L, Mo T, Dong W, Zhong X, Woods C, Thielen A, et al. Deep V3 sequencing for HIV type 1 tropism in treatment-naive patients: a reanalysis of the MERIT trial of maraviroc. Clin Infect Dis. 2011;53:732-42 pubmed publisher..Reanalysis of the MERIT trial using deep V3 loop sequencing indicates that, had patients originally been screened using this method, the maraviroc arm would have likely been found to be noninferior to the efavirenz arm. ..
- Hunt P, Shulman N, Hayes T, Dahl V, Somsouk M, Funderburg N, et al. The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial. Blood. 2013;121:4635-46 pubmed publisher..These results may have relevance for trials of maraviroc for HIV preexposure prophylaxis and graft-versus-host disease. This trial was registered at www.clinicaltrials.gov as #NCT00735072. ..
- Gauthier L, Potter D, Hebert C, Letcher R. Temporal trends and spatial distribution of non-polybrominated diphenyl ether flame retardants in the eggs of colonial populations of Great Lakes herring gulls. Environ Sci Technol. 2009;43:312-7 pubmed
- Funderburg N, Kalinowska M, Eason J, Goodrich J, Heera J, Mayer H, et al. Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4+ cell rises in HIV-infected patients. PLoS ONE. 2010;5:e13188 pubmed publisher..Levels of high-sensitivity C-reactive protein remained constant in the maraviroc arm and increased in the efavirenz arm. Decreases in immune activation correlated with increased CD4(+) T cell gains. ClinicalTrials.gov NCT00098293. ..
- Kondru R, Zhang J, Ji C, Mirzadegan T, Rotstein D, Sankuratri S, et al. Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists. Mol Pharmacol. 2008;73:789-800 pubmed..The fully mapped binding pocket of CCR5 is being used for structure-based design and lead optimization of novel anti-HIV CCR5 inhibitors with improved potency and better resistance profile. ..
- Emmelkamp J, Rockstroh J. CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature. Eur J Med Res. 2007;12:409-17 pubmed..Extended follow-up of the vicriviroc trials showed no further case of malignancy, reassuring the overall good tolerability profile of the drug so far. ..
- Kim Y, An J, Jin Y, Rhee Y, Cha B, Lee H, et al. Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732. J Mol Endocrinol. 2007;38:455-65 pubmed..These results should be carefully verified to assess the utility of CKD-732 as an anti-obesity drug. ..
- Ananthalakshmi K, Edafiogho I, Kombian S. Concentration-dependent effects of anticonvulsant enaminone methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate on neuronal excitability in vitro. Neuroscience. 2006;141:345-56 pubmed..These two actions of methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate on neuronal excitability would have therapeutic implications in future clinical use of enaminones as anticonvulsants in seizure disorders. ..
- Rosario M, Jacqmin P, Dorr P, van der Ryst E, Hitchcock C. A pharmacokinetic-pharmacodynamic disease model to predict in vivo antiviral activity of maraviroc. Clin Pharmacol Ther. 2005;78:508-19 pubmed..This model was a powerful tool for assisting in the design of clinical studies on new agents for treating HIV/acquired immunodeficiency syndrome. ..
- Cooper D, Heera J, Goodrich J, Tawadrous M, Saag M, DeJesus E, et al. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis. 2010;201:803-13 pubmed publisher..Their retrospective exclusion resulted in similar response rates in both arms Trial registration. ClinicalTrials.gov identifier: (NCT00098293) . ..
- Abel S, Davis J, Ridgway C, Hamlin J, Vourvahis M. Pharmacokinetics, safety and tolerability of a single oral dose of maraviroc in HIV-negative subjects with mild and moderate hepatic impairment. Antivir Ther. 2009;14:831-7 pubmed publisher..The single 300 mg dose of maraviroc was well tolerated by subjects with normal and impaired hepatic function. ..
- Sterjovski J, Roche M, Churchill M, Ellett A, Farrugia W, Gray L, et al. An altered and more efficient mechanism of CCR5 engagement contributes to macrophage tropism of CCR5-using HIV-1 envelopes. Virology. 2010;404:269-78 pubmed publisher..Thus, enhanced gp120-CCR5 interactions may contribute to M-tropism of R5 HIV-1 strains through different structural mechanisms...
- Tilton J, Doms R. Entry inhibitors in the treatment of HIV-1 infection. Antiviral Res. 2010;85:91-100 pubmed publisher..This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. ..
- Fatkenheuer G, Pozniak A, Johnson M, Plettenberg A, Staszewski S, Hoepelman A, et al. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat Med. 2005;11:1170-2 pubmed..6 log(10) copies/ml at all twice daily doses >or=100 mg. These results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach. ..
- Symons J, van Lelyveld S, Hoepelman A, van Ham P, de Jong D, Wensing A, et al. Maraviroc is able to inhibit dual-R5 viruses in a dual/mixed HIV-1-infected patient. J Antimicrob Chemother. 2011;66:890-5 pubmed publisher..This case report demonstrates that dual-tropic viruses, capable of using both co-receptors in phenotypic assays, can be inhibited by maraviroc if they have a CCR5 co-receptor preference in vivo. ..
- Caldwell D, Evans J. Developing clinical role of a CCR5 co-receptor antagonist in HIV-1 infection. Expert Opin Pharmacother. 2008;9:3231-42 pubmed
- Rosario M, Jacqmin P, Dorr P, James I, Jenkins T, Abel S, et al. Population pharmacokinetic/pharmacodynamic analysis of CCR5 receptor occupancy by maraviroc in healthy subjects and HIV-positive patients. Br J Clin Pharmacol. 2008;65 Suppl 1:86-94 pubmed publisher..Based on this analysis, it was decided not to use receptor occupancy as a biomarker of viral load inhibition during the development of CCR5 antagonist compounds. ..
- Méchaï F, Quertainmont Y, Sahali S, Delfraissy J, Ghosn J. Post-exposure prophylaxis with a maraviroc-containing regimen after occupational exposure to a multi-resistant HIV-infected source person. J Med Virol. 2008;80:9-10 pubmed..Post-exposure prophylaxis was well tolerated, with no increase in liver function tests. The health care worker remained HIV-negative after a 6-month follow-up. ..
- Dorr P, Westby M, Dobbs S, Griffin P, Irvine B, Macartney M, 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. 2005;49:4721-32 pubmed..Clinical trials are ongoing to further investigate the potential of using maraviroc for the treatment of HIV-1 infection and AIDS. ..
- Recordon Pinson P, Soulie C, Flandre P, Descamps D, Lazrek M, Charpentier C, et al. Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study. Antimicrob Agents Chemother. 2010;54:3335-40 pubmed publisher..The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist. ..
- Walker D, Bowers S, Mitchell R, Potchoiba M, Schroeder C, Small H. Preclinical assessment of the distribution of maraviroc to potential human immunodeficiency virus (HIV) sanctuary sites in the central nervous system (CNS) and gut-associated lymphoid tissue (GALT). Xenobiotica. 2008;38:1330-9 pubmed
- Napier C, Sale H, Mosley M, Rickett G, Dorr P, Mansfield R, et al. Molecular cloning and radioligand binding characterization of the chemokine receptor CCR5 from rhesus macaque and human. Biochem Pharmacol. 2005;71:163-72 pubmed
- Nahari D, Satchi Fainaro R, Chen M, Mitchell I, Task L, Liu Z, et al. Tumor cytotoxicity and endothelial Rac inhibition induced by TNP-470 in anaplastic thyroid cancer. Mol Cancer Ther. 2007;6:1329-37 pubmed..In endothelial cells, TNP-470 prevented vascular endothelial growth factor-induced endothelial permeability, intercellular gap formation, and ruffle formation by preventing Rac1 activation. ..
- Nauwelaerts K, Fisher M, Froeyen M, Lescrinier E, Aerschot A, Xu D, et al. Structural characterization and biological evaluation of small interfering RNAs containing cyclohexenyl nucleosides. J Am Chem Soc. 2007;129:9340-8 pubmed..This was tested by targeting inhibition of expression of the MDR1 gene with accompanying changes in P-glycoprotein expression, drug transport, and drug resistance. ..
- Moore J, Kuritzkes D. A pièce de resistance: how HIV-1 escapes small molecule CCR5 inhibitors. Curr Opin HIV AIDS. 2009;4:118-24 pubmed publisher..HIV-1 escapes small molecule CCR5 inhibitors by continuing to use CCR5 in an inhibitor-insensitive manner, or evades them by expanding naturally insensitive, CXCR4-using variants. ..
- Westby M, Smith Burchnell C, Mori J, Lewis M, Mosley M, Stockdale M, et al. Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. J Virol. 2007;81:2359-71 pubmed..This hypothesis was further corroborated by the observation that a high concentration of maraviroc blocks the activity of aplaviroc against maraviroc-resistant virus. ..
- Yamaguchi J, Hayashi Y. Syntheses of fumagillin and ovalicin. Chemistry. 2010;16:3884-901 pubmed publisher..Despite the relatively small size of these molecules, their syntheses highlight the efficient construction of stereogenic centers in organic synthesis. ..
- Yilmaz A, Watson V, Else L, Gisslen M. Cerebrospinal fluid maraviroc concentrations in HIV-1 infected patients. AIDS. 2009;23:2537-40 pubmed publisher..63 ng/ml (range 1.83-12.2). CSF samples exceeded the median EC90 for maraviroc (0.57 ng/ml) by at least three-fold. The CSF levels of maraviroc found in this study likely contribute to viral suppression in the CSF. ..
- Melica G, Canestri A, Peytavin G, Lelievre J, Bouvier Alias M, Clavel C, et al. Maraviroc-containing regimen suppresses HIV replication in the cerebrospinal fluid of patients with neurological symptoms. AIDS. 2010;24:2130-3 pubmed publisher..Four patients had CSF concentrations above the protein-adjusted inhibitory concentration (IC90) of 0.57 ng/ml (0.06-10.7) with a median of 102 ng/ml (35-173). ..
- Hunt J, Romanelli F. Maraviroc, a CCR5 coreceptor antagonist that blocks entry of human immunodeficiency virus type 1. Pharmacotherapy. 2009;29:295-304 pubmed publisher..Long-term studies with both targets are required to explore the critical issues of efficacy and immunologic safety, as the function of these coreceptors is linked to host chemokine pathways. ..
- Kromdijk W, Huitema A, Mulder J. Treatment of HIV infection with the CCR5 antagonist maraviroc. Expert Opin Pharmacother. 2010;11:1215-23 pubmed publisher..Also, maraviroc will be an attractive option for HIV-1-infected treatment-naive patients with R5-tropic viruses only, once genotypic assays have been validated. ..
- Abel S, Back D, Vourvahis M. Maraviroc: pharmacokinetics and drug interactions. Antivir Ther. 2009;14:607-18 pubmed
- Tomy G, Pleskach K, Arsenault G, Potter D, McCrindle R, Marvin C, et al. Identilication of the novel cycloaliphatic brominated flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane in Canadian Arctic beluga (Delphinapterus leucas). Environ Sci Technol. 2008;42:543-9 pubmed..Observed concentrations of the beta-isomer as measured by HRMS ranged from 1.1 to 9.3 ng/g (lipid weight). ..
- Vandekerckhove L, Verhofstede C, Vogelaers D. Maraviroc: integration of a new antiretroviral drug class into clinical practice. J Antimicrob Chemother. 2008;61:1187-90 pubmed publisher..We discuss the challenges associated with the currently available assay, as well as the potential role of alternative assays. ..
- Arsenault G, Lough A, Marvin C, McAlees A, McCrindle R, MacInnis G, et al. Structure characterization and thermal stabilities of the isomers of the brominated flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane. Chemosphere. 2008;72:1163-70 pubmed publisher..Although technical TBECH does not contain the gamma- and delta-isomers, they may still be relevant environmental contaminants since manufacturing processes utilize thermal processes which may induce their formation. ..
- Soulie C, Malet I, Lambert Niclot S, Tubiana R, Thévenin M, Simon A, et al. Primary genotypic resistance of HIV-1 to CCR5 antagonists in CCR5 antagonist treatment-naive patients. AIDS. 2008;22:2212-4 pubmed publisher..The V3 loop region was rather polymorphic, and 7.3% of patients showed viruses with combinations of mutations in V3 loop previously described to be involved in maraviroc resistance, a licensed CCR5 antagonist. ..
- Yost R, Pasquale T, Sahloff E. Maraviroc: a coreceptor CCR5 antagonist for management of HIV infection. Am J Health Syst Pharm. 2009;66:715-26 pubmed publisher..Available data support the use of maraviroc, the first CCR5 antagonist to receive FDA marketing approval, as part of an optimized antiretroviral regimen in treatment-experienced patients infected with CCR5-tropic HIV. ..
- Archer J, Braverman M, Taillon B, Desany B, James I, Harrigan P, et al. Detection of low-frequency pretherapy chemokine (CXC motif) receptor 4 (CXCR4)-using HIV-1 with ultra-deep pyrosequencing. AIDS. 2009;23:1209-18 pubmed publisher..The evolutionary analysis demonstrates the extent of diversity present at a single time point within an infected individual and the rapid effect of drug pressure on the structure of a viral population. ..
- Li J, Chen G, Ye P, Wang S, Zhang K, Chen W, et al. CCR5 blockade in combination with cyclosporine increased cardiac graft survival and generated alternatively activated macrophages in primates. J Immunol. 2011;186:3753-61 pubmed publisher..In conclusion, MVC/CsA protects cardiac allograft in primates and this effect is associated with generating AAMs through activation of the PPAR? nuclear receptor. ..
- Saag M, Goodrich J, Fatkenheuer G, Clotet B, Clumeck N, Sullivan J, et al. A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1. J Infect Dis. 2009;199:1638-47 pubmed publisher..Clinicaltrials.gov identifier NCT00098748 . ..
- Abel S, Russell D, Taylor Worth R, Ridgway C, Muirhead G. Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol. 2008;65 Suppl 1:27-37 pubmed publisher..TPV/r does not affect the steady-state pharmacokinetics of maraviroc, and hence no dose adjustment would be warranted. ..
- Abel S, van der Ryst E, Rosario M, Ridgway C, Medhurst C, Taylor Worth R, et al. Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers. Br J Clin Pharmacol. 2008;65 Suppl 1:5-18 pubmed publisher..It does not significantly influence the activity of major drug-metabolizing enzymes and is well tolerated at clinically relevant doses, with most adverse events being mild or moderate. ..
- Westby M, Lewis M, Whitcomb J, Youle M, Pozniak A, James I, et al. Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. J Virol. 2006;80:4909-20 pubmed..Importantly, in all three patients, circulating virus reverted to predominantly CCR5 tropic following cessation of maraviroc. ..
- Perry C. Maraviroc: a review of its use in the management of CCR5-tropic HIV-1 infection. Drugs. 2010;70:1189-213 pubmed publisher..Available data indicate that maraviroc may also have a role in treatment-naive adults with CCR5-tropic HIV-1 infection, a population in whom CCR5-tropic HIV-1 is often the major quasispecies. ..