Perifosine
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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 Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
structurally related to
miltefosine Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as '' Naegleria fowleri'' and '' Balamuthia mandrillaris''. This includes the three forms of ...
. Perifosine interrupts the
PI3K/AKT/mTOR pathway The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates ...
by acting as an
allosteric In the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the p ...
AKT inhibitor targeting the
pleckstrin homology domain Pleckstrin homology domain (PH domain) or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton. This domain can bind phosph ...
of AKT. It was being developed by Keryx Biopharmaceuticals who had licensed it from Æterna Zentaris Inc.Smartoncology newsletter
, Feb 2010
In 2010, perifosine received
orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...
status in the U.S. for the treatment of multiple myeloma and
neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the head, neck, chest, abdomen, or Vertebral column, spine. Symptoms may include ...
, and for multiple myeloma in the EU. However, both were later withdrawn. In 2011 it was in a phase III trial for
colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
, and another for
multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...
. On April 2, 2012, it was announced that perifosine failed its phase III clinical trial for treatment of colon cancer. Detailed results were released in June 2012. 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.


References

{{reflist Abandoned drugs Experimental drugs Organophosphates Phospholipids Protein kinase inhibitors Quaternary ammonium compounds Withdrawn drugs Zwitterions