Perifosine

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]

Perifosine
Names
IUPAC name
1,1-Dimethylpiperidinium-4-yl octadecyl phosphate
Other names
D 21266; KRX 0401
Identifiers
CAS Number
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.217.789
PubChem CID
UNII
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
SMILES
  • [O-]P(=O)(OCCCCCCCCCCCCCCCCCC)OC1CC[N+](C)(C)CC1
Properties
Chemical formula
 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).
Infobox references

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the treatment of multiple myeloma and neuroblastoma, and for multiple myeloma in the EU.[4] However, both were later withdrawn.[5][6]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. Mol Cancer Ther. 2 (11): 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. "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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