Aplaviroc

Last updated
Aplaviroc
Aplaviroc structure.svg
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
Formula C33H43N3O6
Molar mass 577.722 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 Yes check.svgY
  • Key:GWNOTCOIYUNTQP-FQLXRVMXSA-N Yes check.svgY
   (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.

Contents

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

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References

  1. Borthwick AD (July 2012). "2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products". Chemical Reviews. 112 (7): 3641–716. 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 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): 2087–96. 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): 858–65. doi:10.1128/aac.00821-07. PMC   2258506 . 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 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.

Further reading