Aplaviroc
{{Infobox drug | verifiedrevid = 451871816 | 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 | image = Aplaviroc.svg | width = 300
| pregnancy_category = ? | legal_status = ? | routes_of_administration = Oral
| bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion =
| IUPHAR_ligand = 805
| CAS_number_Ref = 
| CAS_number = 461023-63-2
| ATC_prefix = none
| ATC_suffix =
| PubChem = 3001322
| ChEMBL = 1255794
| DrugBank_Ref =
| DrugBank =
| ChemSpiderID_Ref =
| ChemSpiderID = 2272720
| UNII_Ref =
| UNII = 98B425P30V
| KEGG_Ref =
| KEGG = D06557
| C=33 | H=43 | N=3 | O=6
| molecular_weight = 577.711 g/mol
| smiles = 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
| StdInChI_Ref =
| StdInChI = 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
| StdInChIKey_Ref =
| StdInChIKey = GWNOTCOIYUNTQP-FQLXRVMXSA-N
}}
Aplaviroc (INN, codenamed AK602 and GSK-873140) is a CCR5 entry inhibitor developed for the treatment of HIV infection.[1][2] It was 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
References
- ^ 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.
{{cite web}}: Unknown parameter|deadurl=ignored (|url-status=suggested) (help) - ^ 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.
- ^ "Aplaviroc (GSK-873,140)". AIDSmeds.com. October 25, 2005. Retrieved September 5, 2008.[dead link]
- ^ 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.
- ^ 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.
{{cite web}}: Unknown parameter|deadurl=ignored (|url-status=suggested) (help) - ^ 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
- 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.
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