Aplaviroc

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Aplaviroc
Aplaviroc.svg
Systematic (IUPAC) name
4-(4-{[(3R)-1-butyl-3-[(R)-cyclohexylhydroxymethyl]-2,5-dioxo- 1,4,9-triazaspiro[5.5]undecan-9-yl]methyl}phenoxy)benzoic acid
Clinical data
Legal status ?
Identifiers
CAS number 461023-63-2 YesY
ATC code None
PubChem CID 3001322
ChemSpider 2272720 YesY
UNII 98B425P30V YesY
KEGG D06557 YesY
ChEMBL CHEMBL1255794
Chemical data
Formula C33H43N3O6 
Mol. mass 577.711 g/mol
 YesY (what is this?)  (verify)

Aplaviroc (INN, codenamed AK602 and GSK-873140) is a CCR5 entry inhibitor developed for the treatment of HIV infection.[1][2] It is developed by GlaxoSmithKline.

In October 2005, all studies of aplaviroc were discontinued due to liver toxicity concerns.[3][4] Some authors have claimed that evidence of poor efficacy may have contributed to termination of the drug's development;[5] the ASCENT study, one of the discontinued trials, showed aplaviroc to be under-effective in many patients even at high concentrations.[6]

See also[edit]

References[edit]

  1. ^ Maeda, Kenji; Ogata, Hiromi; Harada, Shigeyoshi et al. (2004). "Determination of binding sites of a unique CCR5 inhibitor AK602 / ONO-4128/ GW873140 on human CCR5" (PDF). Conference on Retroviruses and Opportunistic Infections. Archived from the original on November 3, 2005. 
  2. ^ Nakata, Hirotomo; Maeda, Kenji; Miyakawa, Toshikazu et al. (February 2005). "Potent Anti-R5 Human Immunodeficiency Virus Type 1 Effects of a CCR5 Antagonist, AK602/ONO4128/GW873140, in a Novel Human Peripheral Blood Mononuclear Cell Nonobese Diabetic-SCID, Interleukin-2 Receptor γ-Chain-Knocked-Out AIDS Mouse Model". Journal of Virology 79 (4): 2087–96. doi:10.1128/jvi.79.4.2087-2096.2005. 
  3. ^ "Aplaviroc (GSK-873,140)". AIDSmeds.com. October 25, 2005. Retrieved September 5, 2008. [dead link]
  4. ^ Nichols WG, Steel HM, Bonny T et al. (March 2008). "Hepatotoxicity Observed in Clinical Trials of Aplaviroc (GW873140)". Antimicrobial Agents and Chemotherapy 52 (3): 858–65. doi:10.1128/aac.00821-07. PMC 2258506. PMID 18070967. 
  5. ^ Moyle, Graeme (December 19, 2006). "The Last Word on Aplaviroc: A CCR5 Antagonist With Poor Efficacy". The Body. Archived from the original on 6 October 2008. Retrieved September 5, 2008. 
  6. ^ Currier, Judith; Lazzarin, Adriano; Sloan, Louis et al. (2008). "Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study". Antiviral Therapy (Lond.) 13 (2): 297–306. PMID 18505181. 

Further reading[edit]

  • Horster, S; Goebel, FD (April 2006). "Serious doubts on safety and efficacy of CCR5 antagonists: CCR5 antagonists teeter on a knife-edge". Infection 34 (2): 110–13. doi:10.1007/s15010-006-6206-1. PMID 16703305.