Aplaviroc

{{Short description|Chemical compound}}

{{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 structure.svg

| width = 300

| pregnancy_category =

| legal_status = Development terminated

| routes_of_administration = Oral

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| index2_label = HCl

| CAS_number2_Ref = {{cascite|correct|CAS}}

| CAS_number2 = 461023-63-2

| UNII2_Ref = {{fdacite|correct|FDA}}

| UNII2 = 04D148Z3VR

| IUPHAR_ligand = 805

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 461443-59-4

| ATC_prefix = none

| ATC_suffix =

| PubChem = 3001322

| ChEMBL = 1255794

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 2272720

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 98B425P30V

| KEGG_Ref = {{keggcite|correct|kegg}}

| 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_Ref = {{stdinchicite|correct|chemspider}}

| 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 = {{stdinchicite|correct|chemspider}}

| 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{{cite journal | vauthors = Borthwick AD | title = 2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products | journal = Chemical Reviews | volume = 112 | issue = 7 | pages = 3641–3716 | date = July 2012 | pmid = 22575049 | doi = 10.1021/cr200398y }} developed for the treatment of HIV infection.{{cite conference | vauthors = Maeda K, Ogata H, Harada S, Tojo Y, Miyakawa T, Nakata H, Takaoka Y, Shibayama S, Sagawa K, Daikichi F, Moravek J | display-authors = 6 | title = Determination of binding sites of a unique CCR5 inhibitor AK602 on human CCR5 | conference = 11th conference on retroviruses and opportunistic infections | location = San Francisco, CA | date = 2004 |url= http://www.retroconference.org/2004/cd/PDFs/540.pdf |archive-url=https://web.archive.org/web/20051103110511/http://www.retroconference.org/2004/cd/PDFs/540.pdf |archive-date=November 3, 2005 }}{{cite journal | vauthors = Nakata H, Maeda K, Miyakawa T, Shibayama S, Matsuo M, Takaoka Y, Ito M, Koyanagi Y, Mitsuya H | display-authors = 6 | title = 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 = Journal of Virology | volume = 79 | issue = 4 | pages = 2087–2096 | date = February 2005 | pmid = 15681411 | pmc = 546550 | doi = 10.1128/jvi.79.4.2087-2096.2005 }} It was developed by GlaxoSmithKline.

In October 2005, all studies of aplaviroc were discontinued due to liver toxicity concerns.{{cite web|url=http://www.aidsmeds.com/drugs/aplaviroc.htm |title=Aplaviroc (GSK-873,140) |date=October 25, 2005 |publisher=AIDSmeds.com |access-date=September 5, 2008 |url-status=dead |archive-url=https://web.archive.org/web/20070113173331/http://www.aidsmeds.com/drugs/aplaviroc.htm |archive-date=January 13, 2007 }}{{cite journal | vauthors = Nichols WG, Steel HM, Bonny T, Adkison K, Curtis L, Millard J, Kabeya K, Clumeck N | display-authors = 6 | title = Hepatotoxicity observed in clinical trials of aplaviroc (GW873140) | journal = Antimicrobial Agents and Chemotherapy | volume = 52 | issue = 3 | pages = 858–865 | date = March 2008 | pmid = 18070967 | pmc = 2258506 | doi = 10.1128/aac.00821-07 }} Some authors have claimed that evidence of poor efficacy may have contributed to termination of the drug's development;{{cite web |url=http://www.thebody.com/content/treat/art39205.html |title=The Last Word on Aplaviroc: A CCR5 Antagonist With Poor Efficacy |date=December 19, 2006 | vauthors = Moyle G |publisher=The Body |access-date=September 5, 2008 |archive-url=https://web.archive.org/web/20081006093337/http://www.thebody.com/content/treat/art39205.html |archive-date=6 October 2008 |url-status=dead }} the ASCENT study, one of the discontinued trials, showed aplaviroc to be under-effective in many patients even at high concentrations.{{cite journal | vauthors = Currier J, Lazzarin A, Sloan L, Clumeck N, Slims J, McCarty D, Steel H, Kleim JP, Bonny T, Millard J | display-authors = 6 | title = Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study | journal = Antiviral Therapy | volume = 13 | issue = 2 | pages = 297–306 | year = 2008 | pmid = 18505181 | doi = 10.1177/135965350801300204 | s2cid = 21839689 | doi-access = free }}