Perifosine

Last updated
Perifosine
Perifosine.svg
Perifosine-zwitterion-3D-spacefill.png
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 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
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 [4] However, both were later withdrawn.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. 1 2 "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". Archived from the original on March 2, 2022.
  6. ↑ "EU/3/10/740: Orphan designation for the treatment of multiple myeloma: Perifosine". 17 September 2018.
  7. ↑ "Perifosine Plus Capecitabine Versus Placebo Plus Capecitabine in Patients with Refractory Advanced Colorectal Cancer - Full Text View - ClinicalTrials.gov". Archived from the original on 2011-07-27. Retrieved 2011-03-24.
  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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