Aplaviroc

Aplaviroc
Clinical data
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • Development terminated
Identifiers
  • 4-(4-{[(3R)-1-butyl-3-[(R)-cyclohexylhydroxymethyl]-2,5-dioxo- 1,4,9-triazaspiro[5.5]undecan-9-yl]methyl}phenoxy)benzoic acid
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC33H43N3O6
Molar mass577.722 g·mol−1
3D model (JSmol)
  • CCCCN1C(=O)[C@H](NC(=O)C12CCN(CC2)CC3=CC=C(C=C3)OC4=CC=C(C=C4)C(=O)O)[C@@H](C5CCCCC5)O
  • InChI=1S/C33H43N3O6/c1-2-3-19-36-30(38)28(29(37)24-7-5-4-6-8-24)34-32(41)33(36)17-20-35(21-18-33)22-23-9-13-26(14-10-23)42-27-15-11-25(12-16-27)31(39)40/h9-16,24,28-29,37H,2-8,17-22H2,1H3,(H,34,41)(H,39,40)/t28-,29-/m1/s1 checkY
  • Key:GWNOTCOIYUNTQP-FQLXRVMXSA-N checkY
  (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]

  1. ^ Borthwick AD (July 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 K, Ogata H, Harada S, Tojo Y, Miyakawa T, Nakata H, et al. (2004). Determination of binding sites of a unique CCR5 inhibitor AK602 on human CCR5 (PDF). 11th conference on retroviruses and opportunistic infections. San Francisco, CA. Archived from the original (PDF) on November 3, 2005.
  3. ^ Nakata H, Maeda K, Miyakawa T, Shibayama S, Matsuo M, Takaoka Y, 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 gamma-chain-knocked-out AIDS mouse model". Journal of Virology. 79 (4): 2087–2096. doi:10.1128/jvi.79.4.2087-2096.2005. PMC 546550. 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, Adkison K, Curtis L, Millard J, et al. (March 2008). "Hepatotoxicity observed in clinical trials of aplaviroc (GW873140)". Antimicrobial Agents and Chemotherapy. 52 (3): 858–865. doi:10.1128/aac.00821-07. PMC 2258506. PMID 18070967.
  6. ^ Moyle G (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 J, Lazzarin A, Sloan L, Clumeck N, Slims J, McCarty D, et al. (2008). "Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study". Antiviral Therapy. 13 (2): 297–306. doi:10.1177/135965350801300204. PMID 18505181. S2CID 21839689.