perifosine
{{chembox
| ImageFile = Perifosine.svg
| ImageSize = 320
| ImageAlt = Skeletal formula of perifosine
| ImageFile1 = Perifosine-zwitterion-3D-spacefill.png
| 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
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|Section3={{Chembox Hazards
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|Section5={{Chembox Pharmacology
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Perifosine (also KRX-0401) is a former drug candidate that was under development for a variety of cancer indications. It is an alkyl-phospholipid{{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}} 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.{{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}} It was being developed by Keryx Biopharmaceuticals who had licensed it from Æterna Zentaris Inc.[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
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. However, both were later withdrawn.{{cite web|title=FDA Orphan Drug Designations and Approvals: Perifosine|url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=310010}}{{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}}
In 2011 it was in a phase III trial for colorectal cancer,{{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 }} and another for multiple myeloma.{{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 }}{{ClinicalTrialsGov|NCT01002248|Assessment of Efficacy and Safety of Perifosine, Bortezomib and Dexamethasone in Multiple Myeloma Patients}} On April 2, 2012, it was announced that perifosine failed its phase III clinical trial for treatment of colon cancer.{{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 }} Detailed results were released in June 2012.{{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 }} 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.{{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 }}