Atiprimod
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| Systematic (IUPAC) name | |
|---|---|
| 3-(8,8-dipropyl-3-azaspiro[4.5]decan-3-yl)-N,N- diethylpropan-1-amine | |
| Clinical data | |
| Identifiers | |
123018-47-3  | |
| None | |
| PubChem | CID 129869 |
| ChemSpider |
114962  |
| UNII |
MG7D3QD743 |
| ChEMBL |
CHEMBL103735 |
| Chemical data | |
| Formula | C22H44N2 |
| 336.598 g/mol | |
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SMILES
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| (what is this?) (verify) | |
Atiprimod (INN, codenamed SK&F106615) is a substance being studied in the treatment of certain multiple myelomas and other advanced cancers. It may block the growth of tumors and the growth of blood vessels from surrounding tissue to the tumor. This drug is also being developed by AnorMED as a potential treatment for rheumatoid arthritis and other autoimmune diseases. It was first developed by SmithKline Beecham (now part of GlaxoSmithKline) as a potential treatment for rheumatoid arthritis.[1] The substance is also known as azaspirane, although this more properly refers to the class of chemicals to which atiprimod belongs.
History
Phase I trials have been successfully completed and Phase II multi-center trials have been approved by the FDA. The compound was discovered in a joint research and development program with SmithKline and French (now SmithKline Beecham, SB) but following acceptance of the Phase II protocol by the FDA, SB decided not to proceed with further development of atiprimod as a result of an internal restructuring program. All rights to atiprimod and other azaspiranes developed in this program have reverted to AnorMED. The compound was originally disclosed in European patent, EP-00310321, entitled 'Preparation of N-aminoalkyl-2-azaspiro[4.5]decanes and analogs as immunosuppressants', while a cost-effective, efficacious pilot plant synthesis has also been described. On January 7, 2008 Callisto Pharmaceuticals, Inc. announced that it has restructured its license agreement with Genzyme Corporation for Atiprimod. In August 2002, Callisto’s wholly owned subsidiary, Synergy, acquired from AnorMED Inc. worldwide exclusive rights to develop, manufacture and commercialize Atiprimod. AnorMED was acquired by Genzyme in November 2006.
The restructured agreement eliminates all milestone payments and reduces royalties owed to Genzyme to single digits. In return for the reduced future payments to Genzyme, Callisto is paying an upfront fee in 2008.
Synergy Pharmaceuticals, Inc. (a wholly owned subsidiary of Callisto) entered into a license agreement with AnorMED Inc. to license Atiprimod from AnorMED.
Mechanism of action
Atiprimod is a cationic amphiphilic compound. It has been shown to inhibit angiogenesis in a developmental blood vessel model using chicken eggs, as well. It is thought to inhibit the secretion of VEGF - a growth factor that promotes such angiogenesis.
Separately, this compound has shown anti-MCL (Mantle Cell Lymphoma) activity via cellular apotosis.[2]
Synthesis
References
- ↑ Jacobs GS (Spring 2004). "Atiprimod: A New Drug Candidate in Early-Stage Development for Myeloma". Myeloma Today (International Myeloma Foundation) 5 (10). Retrieved on September 14, 200.
- ↑ Wang, Michael, et al, "Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways", Blood, June 15, 2007, vol. 109, No. 12, pp. 5455-5462.
Further reading
- Hamasaki M, Hideshima T, Tassone P et al. (June 2005). "Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro 4.5 decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo". Blood 105 (11): 4470–6. doi:10.1182/blood-2004-09-3794. PMC 1895034. PMID 15705788.
External links
- Atiprimod entry in the public domain NCI Dictionary of Cancer Terms
This article incorporates public domain material from the U.S. National Cancer Institute document "Dictionary of Cancer Terms".