Perifosine (KRX-0401)

• CAT Number: I002001
• CAS Number: 157716-52-4
• Molecular Formula: C₂₅H₅₃NO₄P
• Molecular Weight: 462.66
• Purity: ≥95%
• Synonyms: (1,1-dimethylpiperidin-1-ium-4-yl) octadecyl phosphate
• Target: Akt
• Solubility: H2O: 125 mg/mL, DMSO: ＜ 1.2 mg/mL
• Storage: 3 years -20C powder
• 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/p+1
• InChIKey: SZFPYBIJACMNJV-UHFFFAOYSA-O
• SMILES: CCCCCCCCCCCCCCCCCCOP(=O)(O)OC1CC[N+](CC1)(C)C

Perifosine (KRX-0401; D-21266; NSC 639966) is a novel Akt inhibitor with IC50 of 4.7 μM, targets pleckstrin homology domain of Akt.IC50 value:Target: Aktin vitro: Perifosine develops anti-proliferative properties with IC50 of 0.6-8.9 μM in immortalized keratinocytes (HaCaT), and head and neck squamous carcinoma cells [1]. Perifosine strongly reduces phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk) 1/2, induces cell cycle arrest in G1 and G2, and causes dose-dependent growth inhibition of mouse glial progenitors [2]. erifosine (10 μM) completely inhibits the phosphorylation of Akt in MM.1S cells [3].in vivo: Perifosine combining with temozolomide reduces tumor proliferation (a PDGF-driven gliomagenesis) in vivo. The results indicate that Perifosine is an effective drug in gliomas in which Akt and Ras-Erk 1/2 pathways are frequently activated, and may be new candidate for glima treatment in the clinic [2]. Both oral daily and weekly administration of Perifosine significantly reduce human MM tumor growth and increase survival, compared with control animals treated with PBS vehicle only [3].

Reference

1:Phase I study of perifosine monotherapy in patients with recurrent or refractory neuroblastoma. Matsumoto K, Shichino H, Kawamoto H, Kosaka Y, Chin M, Kato K, Mugishima H.Pediatr Blood Cancer. 2017 May 18. doi: 10.1002/pbc.26623. [Epub ahead of print] PMID: 28521076 2:Triggering of Eryptosis, the Suicidal Erythrocyte Death, by Perifosine. Egler J, Lang F.Cell Physiol Biochem. 2017 May 4;41(6):2534-2544. doi: 10.1159/000475977. [Epub ahead of print] PMID: 28472790 Free Article3:Proteome and Acetylome Analysis Identifies Novel Pathways and Targets Regulated by Perifosine in Neuroblastoma. Gu X, Hua Z, Dong Y, Zhan Y, Zhang X, Tian W, Liu Z, Thiele CJ, Li Z.Sci Rep. 2017 Feb 6;7:42062. doi: 10.1038/srep42062. PMID: 28165023 Free PMC Article4:Perifosine Mechanisms of Action in Leishmania Species. López-Arencibia A, Martín-Navarro C, Sifaoui I, Reyes-Batlle M, Wagner C, Lorenzo-Morales J, Maciver SK, Piñero JE.Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e02127-16. doi: 10.1128/AAC.02127-16. Print 2017 Apr. PMID: 28096161 5:A phase I study of perifosine with temsirolimus for recurrent pediatric solid tumors. Becher OJ, Gilheeney SW, Khakoo Y, Lyden DC, Haque S, De Braganca KC, Kolesar JM, Huse JT, Modak S, Wexler LH, Kramer K, Spasojevic I, Dunkel IJ.Pediatr Blood Cancer. 2016 Dec 30. doi: 10.1002/pbc.26409. [Epub ahead of print] PMID: 28035748 6:A phase I/Ib trial targeting the Pi3k/Akt pathway using perifosine: Long-term progression-free survival of patients with resistant neuroblastoma. Kushner BH, Cheung NV, Modak S, Becher OJ, Basu EM, Roberts SS, Kramer K, Dunkel IJ.Int J Cancer. 2017 Jan 15;140(2):480-484. doi: 10.1002/ijc.30440. Epub 2016 Sep 30. PMID: 27649927 7:Perifosine and ABT-737 synergistically inhibit lung cancer cells in vitro and in vivo. Shen J, Xu L, Zhao Q.Biochem Biophys Res Commun. 2016 May 13;473(4):1170-6. doi: 10.1016/j.bbrc.2016.04.035. Epub 2016 Apr 9. PMID: 27073162 8:Modulation of the voltage-gated potassium channel Kv2.1 by the anti-tumor alkylphospholipid perifosine. Delgado-Ramírez M, Morán-Zendejas R, Aréchiga-Figueroa IA, Toro-Castillo C, Ramírez-Martínez JF, Rodríguez-Menchaca AA.Pharmacol Rep. 2016 Apr;68(2):457-61. doi: 10.1016/j.pharep.2015.11.006. Epub 2015 Nov 28. PMID: 26922553 9:Low-concentration of perifosine surprisingly protects cardiomyocytes from oxygen glucose deprivation. Zheng K, Lu H, Sheng Z, Li Y, Xu B.Biochem Biophys Res Commun. 2016 Jan 15;469(3):753-60. doi: 10.1016/j.bbrc.2015.12.014. Epub 2015 Dec 11. PMID: 26686418 10:Perifosine as a potential novel anti-telomerase therapy. Holohan B, Hagiopian MM, Lai TP, Huang E, Friedman DR, Wright WE, Shay JW.Oncotarget. 2015 Sep 8;6(26):21816-26. PMID: 26307677 Free PMC Article