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Perifosine

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Perifosine
Skeletal formula of perifosine
Space-filling model of the perifosine zwitterion
Names
IUPAC name
1,1-Dimethylpiperidinium-4-yl octadecyl phosphate
Other names
D 21266; KRX 0401
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.217.789 Edit this at Wikidata
UNII
  • 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
  • [O-]P(=O)(OCCCCCCCCCCCCCCCCCC)OC1CC[N+](C)(C)CC1
Properties
C25H52NO4P
Molar mass 461.668 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Perifosine (also KRX-0401) is a former drug candidate that was under development for a variety of cancer indications. It is an alkyl-phospholipid[1] 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.[2] It was being developed by Keryx Biopharmaceuticals who had licensed it from Æterna Zentaris Inc.[3]

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the treatment of multiple myeloma and neuroblastoma, and for multiple myeloma in the EU.[4] However, both were later withdrawn.[5][6]

In 2011 it was in a phase III trial for colorectal cancer,[7] and another for multiple myeloma.[4][8] On April 2, 2012, it was announced that perifosine failed its phase III clinical trial for treatment of colon cancer.[9] Detailed results were released in June 2012.[10] 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.[11]

References

  1. ^ Kondapaka; et al. (Nov 2003). "Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation". Molecular Cancer Therapeutics. 2 (11). Mol Cancer Ther: 1093–103. PMID 14617782.
  2. ^ Keane, N. A.; Glavey, S. V.; Krawczyk, J.; O'Dwyer, M. (2014). "AKT as a therapeutic target in multiple myeloma". Expert Opinion on Therapeutic Targets. 18 (8): 897–915. doi:10.1517/14728222.2014.924507. PMID 24905897. S2CID 873910.
  3. ^ Smartoncology newsletter Archived 2011-07-16 at the Wayback Machine, Feb 2010
  4. ^ a b "Yakult Pays Aeterna Zentaris $8.3M for Japanese Rights to Pivotal-Stage Cancer Drug". 9 March 2011.
  5. ^ "FDA Orphan Drug Designations and Approvals: Perifosine".
  6. ^ "EU/3/10/740: Orphan designation for the treatment of multiple myeloma: Perifosine".
  7. ^ "Archived copy". Archived from the original on 2011-07-27. Retrieved 2011-03-24.{{cite web}}: CS1 maint: archived copy as title (link)
  8. ^ Clinical trial number NCT01002248 for "Assessment of Efficacy and Safety of Perifosine, Bortezomib and Dexamethasone in Multiple Myeloma Patients" at ClinicalTrials.gov
  9. ^ "Aeterna Zentaris Regains North American Rights to Akt Inhibitor from Keryx". May 2012.
  10. ^ "Aeterna Zentaris: Phase 3 Data for Perifosine in Colorectal Cancer Presented at ASCO Meeting". 4 June 2012. Archived from the original on 16 January 2013. Retrieved 13 November 2012.
  11. ^ "Æterna Zentaris Inc". Archived from the original on 2014-02-02. Retrieved 2014-01-22.
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