Atiprimod (free base)

WARNING: This product is for research use only, not for human or veterinary use.

Description:Atiprimod is an orally bioavailable small molecule belonging to the azaspirane class of cationic amphiphilic agents with anti-inflammatory, antineoplastic, and antiangiogenic properties. Atiprimod inhibits the phosphorylation of signal transducer and activator of transcription 3 (STAT3), blocking the signalling pathways of interleukin-6 and vascular endothelial growth factor (VEGF) and downregulating the anti-apoptotic proteins Bcl-2, Bcl-XL, and Mcl-1, thereby inhibiting cell proliferation, inducing cell cycle arrest, and inducing apoptosis.

Price and Availability

Atiprimod, purity > 98%,is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200340Name: Atiprimod (free base) CAS#: 123018-47-3Chemical Formula: C22H44N2Exact Mass: 336.35Molecular Weight: 336.61Elemental Analysis:C, 78.50; H, 13.18; N, 8.32

Synonym:azaspirane; SKF 106615SKF 106615SKF106615; SK&F-106615-A-2; SK&F-106615-I-2; SK&F106615A2; SK&F-106615I2

IUPAC/Chemical Name:3-(8,8-dipropyl-3-azaspiro[4.5]decan-3-yl)-N,N- diethylpropan-1-amine

InChi Key:SERHTTSLBVGRBY-UHFFFAOYSA-N

InChi Code:InChI=1S/C22H44N2/c1-5-10-21(11-6-2)12-14-22(15-13-21)16-19-24(20-22)18-9-17-23(7-3)8-4/h5-20H2,1-4H3

SMILES Code:CCN(CC)CCCN1CCC2(CCC(CCC)(CCC)CC2)C1

Technical Data

Additional Information

Atiprimod (INN, code named SK&F106615; also known as azaspirane, although this more properly refers to the class of chemicals to which atiprimod belongs) is a substance being studied in the treatment of certain multiple myelomas and other advanced cancers. Atiprimod may block the growth of tumors and the growth of blood vessels from surrounding tissue to the tumor. Atiprimod is a type of signal transduction inhibitor. It was first developed by SmithKline Beecham (now part of GlaxoSmithKline) as a potential treatment for rheumatoid arthritis. January 7, 2008 Callisto Pharmaceuticals, Inc. announced that it has restructured its license agreement with Genzyme Corporation for Atiprimod. In August 2002, CallistoÂ’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. Atiprimod is a macrophage-targeting oral cytokine inhibitor which is being developed by AnorMED as a potential treatment for rheumatoid arthritis and other autoimmune diseases. Phase I trials have been successfully completed and Phase II multicenter 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. (from http://en.wikipedia.org/wiki/Atiprimod). Related CAS#130065-61-1(Atiprimod dihydrochloride)123018-47-3(Atiprimod free base)  

References

  1: Quintás-Cardama A, Manshouri T, Estrov Z,Harris D, Zhang Y, Gaikwad A, Kantarjian HM, Verstovsek S. Preclinicalcharacterization of atiprimod, a novel JAK2 AND JAK3 inhibitor. InvestNew Drugs. 2010 Apr 7. [Epub ahead of print] PubMed PMID: 20372971.

2: Neri P, Tassone P, Shammas M, Yasui H, Schipani E, Batchu RB, BlottaS, Prabhala R, Catley L, Hamasaki M, Hideshima T, Chauhan D, Jacob GS,Picker D, Venuta S, Anderson KC, Munshi NC. Biological pathways and invivo antitumor activity induced by Atiprimod in myeloma. Leukemia. 2007Dec;21(12):2519-26. Epub 2007 Sep 20. PubMed PMID: 17882285.

3: Wang M, Zhang L, Han X, Yang J, Qian J, Hong S, Samaniego F,Romaguera J, Yi Q. Atiprimod inhibits the growth of mantle cell lymphomain vitro and in vivo and induces apoptosis via activating themitochondrial pathways. Blood. 2007 Jun 15;109(12):5455-62. Epub 2007Feb 22. PubMed PMID: 17317853.

4: Choudhari SR, Khan MA, Harris G, Picker D, Jacob GS, Block T,Shailubhai K. Deactivation of Akt and STAT3 signaling promotesapoptosis, inhibits proliferation, and enhances the sensitivity ofhepatocellular carcinoma cells to an anticancer agent, Atiprimod. MolCancer Ther. 2007 Jan;6(1):112-21. PubMed PMID: 17237271.

5: Kaden S, Reissig HU. Efficient approach to the Azaspirane core of FR901483. Org Lett. 2006 Oct 12;8(21):4763-6. PubMed PMID: 17020297.

6: Shailubhai K. Atiprimod: a multi-functional drug candidate formyeloid and other malignancies. Leuk Res. 2007 Jan;31(1):9-10. Epub 2006Jul 24. PubMed PMID: 16860863.

7: Lakings DB. Atiprimod (AnorMED). IDrugs. 2000 Mar;3(3):329-35. PubMedPMID: 16103943.

8: Amit-Vazina M, Shishodia S, Harris D, Van Q, Wang M, Weber D,Alexanian R, Talpaz M, Aggarwal BB, Estrov Z. Atiprimod blocks STAT3phosphorylation and induces apoptosis in multiple myeloma cells. Br JCancer. 2005 Jul 11;93(1):70-80. PubMed PMID: 15970928; PubMed CentralPMCID: PMC2361492.

9: Faderl S, Ferrajoli A, Harris D, Van Q, Kantarjian HM, Estrov Z.Atiprimod blocks phosphorylation of JAK-STAT and inhibits proliferationof acute myeloid leukemia (AML) cells. Leuk Res. 2007 Jan;31(1):91-5.Epub 2006 Jul 7. PubMed PMID: 16828865.

10: Obniska J, Kamiński K. Lipophilicity characterization of new N-phenylamino-azaspiranesas potential anticonvulsant agents. Biomed Chromatogr. 2006Nov;20(11):1185-91. PubMed PMID: 16799923.