Aplaviroc: Difference between revisions

{{Short description|Chemical compound}}

{{Infobox drug

| verifiedrevid = 451871816

| IUPAC_name = 4-(4-<nowiki/>{[(3''R'')-1-butyl-3-[(''R'')-cyclohexylhydroxymethyl]-2,5-dioxo- 1,4,9-triazaspiro[5.5]undecan-9-yl]methyl}phenoxy)benzoic&nbsp;acid

| image = Aplaviroc structure.svg

| 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_suffix =

| ChEMBL = 1255794

| DrugBank =

| C=33 | H=43 | N=3 | O=6

'''Aplaviroc''' ([[International Nonproprietary Name|INN]], codenamed '''AK602''' and '''GSK-873140''') is a [[CCR5]] [[entry inhibitor]] that belongs to a class of [[2,5-Diketopiperazine|2,5-diketopiperazines]]<ref>{{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 }}</ref> developed for the treatment of [[HIV]] infection.<ref>{{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 }}</ref><ref>{{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 }}</ref> It was developed by [[GlaxoSmithKline]].

In October 2005, all studies of aplaviroc were discontinued due to [[hepatotoxicity|liver toxicity]] concerns.<ref>{{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 }}</ref><ref>{{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 }}</ref> Some authors have claimed that evidence of poor efficacy may have contributed to termination of the drug's development;<ref>{{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 }}</ref> the ASCENT study, one of the discontinued trials, showed aplaviroc to be under-effective in many patients even at high concentrations.<ref>{{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 }}</ref>

== See also ==

* [[CCR5 receptor antagonist]]

== References ==

== Further reading ==

{{refbegin}}

* {{cite journal | vauthors = Horster S, Goebel FD | title = Serious doubts on safety and efficacy of CCR5 antagonists : CCR5 antagonists teeter on a knife-edge | journal = Infection | volume = 34 | issue = 2 | pages = 110–113 | date = April 2006 | pmid = 16703305 | doi = 10.1007/s15010-006-6206-1 | s2cid = 38463200 }}

{{refend}}

{{Antiretroviral drug}}

{{Chemokine receptor modulators}}

[[Category:Abandoned drugs]]

[[Category:Diketopiperazines]]

[[Category:Entry inhibitors]]

[[Category:Hepatotoxins]]

[[Category:Spiro compounds]]

[[Category:Diphenyl ethers]]

[[Category:Butyl compounds]]

{{antiinfective-drug-stub}}