Aplaviroc Explained
| Verifiedrevid: | 451871816 |
| Iupac Name: | 4-(4-phenoxy)benzoic acid |
| Width: | 300 |
| Legal Status: | Development terminated |
| Routes Of Administration: | Oral |
| Index2 Label: | HCl |
| Cas Number2: | 461023-63-2 |
| Unii2: | 04D148Z3VR |
| Iuphar Ligand: | 805 |
| Cas Number: | 461443-59-4 |
| Atc Prefix: | none |
| Pubchem: | 3001322 |
| Chembl: | 1255794 |
| Chemspiderid: | 2272720 |
| Unii: | 98B425P30V |
| Kegg: | D06557 |
| C: | 33 |
| H: | 43 |
| N: | 3 |
| O: | 6 |
| 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: | 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: | GWNOTCOIYUNTQP-FQLXRVMXSA-N |
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
Further reading
- Horster S, Goebel FD . Serious doubts on safety and efficacy of CCR5 antagonists : CCR5 antagonists teeter on a knife-edge . Infection . 34 . 2 . 110–113 . April 2006 . 16703305 . 10.1007/s15010-006-6206-1 . 38463200 .
Notes and References
- Borthwick AD . 2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products . Chemical Reviews . 112 . 7 . 3641–3716 . July 2012 . 22575049 . 10.1021/cr200398y .
- Maeda K, Ogata H, Harada S, Tojo Y, Miyakawa T, Nakata H, Takaoka Y, Shibayama S, Sagawa K, Daikichi F, Moravek J . 6 . Determination of binding sites of a unique CCR5 inhibitor AK602 on human CCR5 . 11th conference on retroviruses and opportunistic infections . San Francisco, CA . 2004 . https://web.archive.org/web/20051103110511/http://www.retroconference.org/2004/cd/PDFs/540.pdf . November 3, 2005 .
- Nakata H, Maeda K, Miyakawa T, Shibayama S, Matsuo M, Takaoka Y, Ito M, Koyanagi Y, Mitsuya H . 6 . 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 . February 2005 . 15681411 . 546550 . 10.1128/jvi.79.4.2087-2096.2005 .
- Web site: Aplaviroc (GSK-873,140) . October 25, 2005 . AIDSmeds.com . September 5, 2008 . dead . https://web.archive.org/web/20070113173331/http://www.aidsmeds.com/drugs/aplaviroc.htm . January 13, 2007 .
- Nichols WG, Steel HM, Bonny T, Adkison K, Curtis L, Millard J, Kabeya K, Clumeck N . 6 . Hepatotoxicity observed in clinical trials of aplaviroc (GW873140) . Antimicrobial Agents and Chemotherapy . 52 . 3 . 858–865 . March 2008 . 18070967 . 2258506 . 10.1128/aac.00821-07 .
- Web site: The Last Word on Aplaviroc: A CCR5 Antagonist With Poor Efficacy . December 19, 2006 . Moyle G . The Body . September 5, 2008 . https://web.archive.org/web/20081006093337/http://www.thebody.com/content/treat/art39205.html . 6 October 2008 . dead .
- Currier J, Lazzarin A, Sloan L, Clumeck N, Slims J, McCarty D, Steel H, Kleim JP, Bonny T, Millard J . 6 . 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 . 2008 . 18505181 . 10.1177/135965350801300204 . 21839689 . free .
