Aplaviroc

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Aplaviroc
Aplaviroc structure.svg
Clinical data
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • Development terminated
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C33H43N3O6
Molar mass 577.711 g/mol
3D model (Jmol)
  (verify)

Aplaviroc (INN, codenamed AK602 and GSK-873140) is a CCR5 entry inhibitor that belongs to a class of 2,5-diketopiperazines[1] developed for the treatment of HIV infection.[2][3] It was developed by GlaxoSmithKline.

In October 2005, all studies of aplaviroc were discontinued due to liver toxicity concerns.[4][5] Some authors have claimed that evidence of poor efficacy may have contributed to termination of the drug's development;[6] the ASCENT study, one of the discontinued trials, showed aplaviroc to be under-effective in many patients even at high concentrations.[7]

See also[edit]

References[edit]

  1. ^ Borthwick AD (2012). "2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products". Chemical Reviews. 112 (7): 3641–3716. doi:10.1021/cr200398y. PMID 22575049. 
  2. ^ 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 (PDF) on November 3, 2005. 
  3. ^ 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. PMC 546550Freely accessible. PMID 15681411. 
  4. ^ "Aplaviroc (GSK-873,140)". AIDSmeds.com. October 25, 2005. Archived from the original on January 13, 2007. Retrieved September 5, 2008. 
  5. ^ 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 2258506Freely accessible. PMID 18070967. 
  6. ^ 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. 
  7. ^ 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.