{{chembox | ImageFile = Perifosine.svg | ImageClass = skin-invert-image | ImageSize = 320 | ImageAlt = Skeletal formula of perifosine | ImageFile1 = Perifosine-zwitterion-3D-spacefill.png | ImageClass1 = bg-transparent | ImageSize1 = 300 | ImageAlt1 = Space-filling model of the perifosine zwitterion | IUPACName = 1,1-Dimethylpiperidinium-4-yl octadecyl phosphate | OtherNames = D 21266; KRX 0401 |Section1={{Chembox Identifiers | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 2GWV496552 | IUPHAR_ligand = 7424 | CASNo = 157716-52-4 | CASNo_Ref = {{cascite|correct|CAS}} | PubChem = 148177 | ChemSpiderID = 130628 | ChEMBL = 372764 | SMILES = [O-]P(=O)(OCCCCCCCCCCCCCCCCCC)OC1CC[N+](C)(C)CC1 | InChI = InChI=1S/C25H52NO4P/c1-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-24-29-31(27,28)30-25-20-22-26(2,3)23-21-25/h25H,4-24H2,1-3H3 }} |Section2={{Chembox Properties | C=25 | H=52 | N=1 | O=4 | P=1 | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = }} |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} |Section5={{Chembox Pharmacology | AdminRoutes = | Bioavail = | Metabolism = | HalfLife = | ProteinBound = | Excretion = | Legal_status = | Legal_US = | Legal_UK = | Legal_AU = | Legal_CA = | PregCat = | PregCat_AU = | PregCat_US = }} }}
'''Perifosine''' (also '''KRX-0401''') is a former drug candidate that was under development for a variety of cancer indications. It is an alkyl-phospholipid<ref name=Kond2003>{{cite journal |url=http://mct.aacrjournals.org/content/2/11/1093.full |title=Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation |date=Nov 2003 |publisher=Mol Cancer Ther |author=Kondapaka|journal=Molecular Cancer Therapeutics |volume=2 |issue=11 |pages=1093–103 |pmid=14617782 |display-authors=etal}}</ref> structurally related to miltefosine. Perifosine interrupts the PI3K/AKT/mTOR pathway by acting as an allosteric AKT inhibitor targeting the pleckstrin homology domain of AKT.<ref name=Keane2014>{{cite journal|pmid=24905897|year=2014|last1=Keane|first1=N. A.|last2=Glavey|first2=S. V.|last3=Krawczyk|first3=J.|last4=O'Dwyer|first4=M.|title=AKT as a therapeutic target in multiple myeloma|journal=Expert Opinion on Therapeutic Targets|volume=18|issue=8|pages=897–915|doi=10.1517/14728222.2014.924507|s2cid=873910}}</ref> It was being developed by Keryx Biopharmaceuticals who had licensed it from Æterna Zentaris Inc.<ref name=SO-2010>[http://smartoncology.com/PDF_Issue2/Smartoncology%20February%2026%20Issue%202.pdf Smartoncology newsletter] {{webarchive|url=https://web.archive.org/web/20110716093309/http://smartoncology.com/PDF_Issue2/Smartoncology%20February%2026%20Issue%202.pdf |date=2011-07-16 }}, Feb 2010</ref>
In 2010, perifosine received orphan drug status in the U.S. for the treatment of multiple myeloma and neuroblastoma, and for multiple myeloma in the EU.<ref name=Mar2011/> However, both were later withdrawn.<ref>{{cite web|title=FDA Orphan Drug Designations and Approvals: Perifosine|url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=310010|archive-url=https://web.archive.org/web/20220302125548/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=310010|url-status=dead|archive-date=March 2, 2022}}</ref><ref>{{cite web|title=EU/3/10/740: Orphan designation for the treatment of multiple myeloma: Perifosine|date=17 September 2018 |url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu310740}}</ref>
In 2011 it was in a phase III trial for colorectal cancer,<ref>{{Cite web |url=http://www.clinicaltrial.gov/ct2/show/NCT01097018 |title=Perifosine Plus Capecitabine Versus Placebo Plus Capecitabine in Patients with Refractory Advanced Colorectal Cancer - Full Text View - ClinicalTrials.gov |access-date=2011-03-24 |archive-date=2011-07-27 |archive-url=https://web.archive.org/web/20110727204029/http://www.clinicaltrial.gov/ct2/show/NCT01097018 |url-status=dead }}</ref> and another for multiple myeloma.<ref name=Mar2011>{{cite news |url=http://www.genengnews.com/gen-news-highlights/yakult-pays-aeterna-zentaris-8-3m-for-japanese-rights-to-pivotal-stage-cancer-drug/81244795/ |title=Yakult Pays Aeterna Zentaris $8.3M for Japanese Rights to Pivotal-Stage Cancer Drug |date=9 March 2011 }}</ref><ref>{{ClinicalTrialsGov|NCT01002248|Assessment of Efficacy and Safety of Perifosine, Bortezomib and Dexamethasone in Multiple Myeloma Patients}}</ref> On April 2, 2012, it was announced that perifosine failed its phase III clinical trial for treatment of colon cancer.<ref name=May2012>{{cite news |url=http://www.genengnews.com/gen-news-highlights/aeterna-zentaris-regains-north-american-rights-to-akt-inhibitor-from-keryx/81246731/ |title=Aeterna Zentaris Regains North American Rights to Akt Inhibitor from Keryx |date=May 2012 }}</ref> Detailed results were released in June 2012.<ref name=AZ201206>{{cite web |url=http://www.aezsinc.com/en/page.php?p=60&q=508 |title=Aeterna Zentaris: Phase 3 Data for Perifosine in Colorectal Cancer Presented at ASCO Meeting |date=4 June 2012 |access-date=13 November 2012 |archive-url=https://archive.today/20130116055911/http://www.aezsinc.com/en/page.php?p=60&q=508 |archive-date=16 January 2013 |url-status=dead }}</ref> On March 11, 2013, Aeterna Zentaris announced the discontinuing of Phase 3 clinical trial of perifosine for the treatment of relapsed and refractory multiple myeloma.<ref>{{Cite web |url=http://www.aezsinc.com/en/page.php?p=60&q=550 |title=Æterna Zentaris Inc |access-date=2014-01-22 |archive-date=2014-02-02 |archive-url=https://web.archive.org/web/20140202132845/http://www.aezsinc.com/en/page.php?p=60&q=550 |url-status=dead }}</ref>
==References== {{reflist}}
Category:Abandoned drugs Category:Experimental drugs Category:Organophosphates Category:Phospholipids Category:Protein kinase inhibitors Category:Quaternary ammonium compounds Category:Withdrawn drugs Category:Zwitterions