WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206777
CAS#: 147817-50-3 (free base)
Description: Siramesine, also known as Lu-28-179, is a potent sigma-2 receptor agonist. Siramesine triggers cell death through destabilisation of mitochondria, but not lysosomes. Siramesine is a lysosomotropic detergent that induces cytoprotective autophagosome accumulation. Siramesine involves lysosomal leakage and oxidative stress.
Hodoodo Cat#: H206777
Name: Siramesine free base
CAS#: 147817-50-3 (free base)
Chemical Formula: C30H31FN2O
Exact Mass: 454.24
Molecular Weight: 454.589
Elemental Analysis: C, 79.26; H, 6.87; F, 4.18; N, 6.16; O, 3.52
Related CAS #: 224177-60-0 (HCl) 147817-50-3 (free base) 163630-79-3 (fumarate)
Synonym: Siramesine free base; Lu-28-179; Lu 28-179; Lu28-179; Lu-28179; Lu 28179; Lu28179.
IUPAC/Chemical Name: 1'-(4-(1-(4-fluorophenyl)-1H-indol-3-yl)butyl)-3H-spiro[isobenzofuran-1,4'-piperidine]
InChi Key: XWAONOGAGZNUSF-UHFFFAOYSA-N
InChi Code: InChI=1S/C30H31FN2O/c31-25-12-14-26(15-13-25)33-21-23(27-9-2-4-11-29(27)33)7-5-6-18-32-19-16-30(17-20-32)28-10-3-1-8-24(28)22-34-30/h1-4,8-15,21H,5-7,16-20,22H2
SMILES Code: FC1=CC=C(N2C=C(CCCCN3CCC4(CC3)OCC5=CC=CC=C45)C6=C2C=CC=C6)C=C1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Related CAS# 224177-60-0 (Siramesine Hydrochloride) 147817-50-3 (Siramesine free base)
| Biological target: | |
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The following data is based on the product molecular weight 454.59 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | |
| In vivo protocol: |
1: Česen MH, Repnik U, Turk V, Turk B. Siramesine triggers cell death through destabilisation of mitochondria, but not lysosomes. Cell Death Dis. 2013 Oct 3;4:e818. doi: 10.1038/cddis.2013.361. PubMed PMID: 24091661; PubMed Central PMCID: PMC3824671.
2: Spirkoski J, Melo FR, Grujic M, Calounova G, Lundequist A, Wernersson S, Pejler G. Mast cell apoptosis induced by siramesine, a sigma-2 receptor agonist. Biochem Pharmacol. 2012 Dec 15;84(12):1671-80. doi: 10.1016/j.bcp.2012.09.028. PubMed PMID: 23058984.
3: Ma S, Henson ES, Chen Y, Gibson SB. Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis. 2016 Jul 21;7:e2307. doi: 10.1038/cddis.2016.208. PubMed PMID: 27441659; PubMed Central PMCID: PMC4973350.
4: Ostenfeld MS, Høyer-Hansen M, Bastholm L, Fehrenbacher N, Olsen OD, Groth-Pedersen L, Puustinen P, Kirkegaard-Sørensen T, Nylandsted J, Farkas T, Jäättelä M. Anti-cancer agent siramesine is a lysosomotropic detergent that induces cytoprotective autophagosome accumulation. Autophagy. 2008 May;4(4):487-99. PubMed PMID: 18305408.
5: Jonhede S, Petersen A, Zetterberg M, Karlsson JO. Acute effects of the sigma-2 receptor agonist siramesine on lysosomal and extra-lysosomal proteolytic systems in lens epithelial cells. Mol Vis. 2010 May 8;16:819-27. PubMed PMID: 20461150; PubMed Central PMCID: PMC2866574.
6: Parry MJ, Alakoskela JM, Khandelia H, Kumar SA, Jäättelä M, Mahalka AK, Kinnunen PK. High-affinity small molecule-phospholipid complex formation: binding of siramesine to phosphatidic acid. J Am Chem Soc. 2008 Oct 1;130(39):12953-60. doi: 10.1021/ja800516w. PubMed PMID: 18767848.
7: Ostenfeld MS, Fehrenbacher N, Høyer-Hansen M, Thomsen C, Farkas T, Jäättelä M. Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress. Cancer Res. 2005 Oct 1;65(19):8975-83. PubMed PMID: 16204071.
8: Zimmermann A, Tian F, Lopez de Diego H, Ringkjøbing Elema M, Rantanen J, Müllertz A, Hovgaard L. Influence of the solid form of siramesine hydrochloride on its behavior in aqueous environments. Pharm Res. 2009 Apr;26(4):846-54. doi: 10.1007/s11095-008-9783-0. PubMed PMID: 19005740.
9: Zimmermann A, Tian F, de Diego HL, Frydenvang K, Rantanen J, Elema MR, Hovgaard L. Structural characterisation and dehydration behaviour of siramesine hydrochloride. J Pharm Sci. 2009 Oct;98(10):3596-607. doi: 10.1002/jps.21679. PubMed PMID: 19156865.
10: Søby KK, Mikkelsen JD, Meier E, Thomsen C. Lu 28-179 labels a sigma(2)-site in rat and human brain. Neuropharmacology. 2002 Jul;43(1):95-100. PubMed PMID: 12213263.
11: Groth-Pedersen L, Ostenfeld MS, Høyer-Hansen M, Nylandsted J, Jäättelä M. Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine. Cancer Res. 2007 Mar 1;67(5):2217-25. PubMed PMID: 17332352.
12: Nielsen AB, Buur A, Larsen C. Bioreversible quaternary N-acyloxymethyl derivatives of the poorly soluble tertiary amine Lu 28-179--synthesis, pharmaceutical chemical characterization and bioavailability studies in dogs. Eur J Pharm Sci. 2005 Dec;26(5):421-8. PubMed PMID: 16150581.
13: Zimmermann A, Millqvist-Fureby A, Elema MR, Hansen T, Müllertz A, Hovgaard L. Adsorption of pharmaceutical excipients onto microcrystals of siramesine hydrochloride: effects on physicochemical properties. Eur J Pharm Biopharm. 2009 Jan;71(1):109-16. doi: 10.1016/j.ejpb.2008.06.014. PubMed PMID: 18619536.
14: Sánchez C, Papp M. The selective sigma2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression. Behav Pharmacol. 2000 Apr;11(2):117-24. PubMed PMID: 10877116.
15: Heading C. Siramesine H Lundbeck. Curr Opin Investig Drugs. 2001 Feb;2(2):266-70. Review. PubMed PMID: 11816842.
16: Sánchez C, Arnt J, Costall B, Kelly ME, Meier E, Naylor RJ, Perregaard J. The selective sigma2-ligand Lu 28-179 has potent anxiolytic-like effects in rodents. J Pharmacol Exp Ther. 1997 Dec;283(3):1323-32. Erratum in: J Pharmacol Exp Ther 1998 May;285(2):929. PubMed PMID: 9400007.
17: Hagforsen E, Paivandy A, Lampinen M, Weström S, Calounova G, Melo FR, Rollman O, Pejler G. Ablation of human skin mast cells in situ by lysosomotropic agents. Exp Dermatol. 2015 Jul;24(7):516-21. doi: 10.1111/exd.12699. PubMed PMID: 25808581.
18: Petersen NH, Olsen OD, Groth-Pedersen L, Ellegaard AM, Bilgin M, Redmer S, Ostenfeld MS, Ulanet D, Dovmark TH, Lønborg A, Vindeløv SD, Hanahan D, Arenz C, Ejsing CS, Kirkegaard T, Rohde M, Nylandsted J, Jäättelä M. Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase. Cancer Cell. 2013 Sep 9;24(3):379-93. doi: 10.1016/j.ccr.2013.08.003. PubMed PMID: 24029234.
19: Skuza G, Rogóz Z. The synergistic effect of selective sigma receptor agonists and uncompetitive NMDA receptor antagonists in the forced swim test in rats. J Physiol Pharmacol. 2006 Jun;57(2):217-29. PubMed PMID: 16845227.
20: Zeng C, Rothfuss JM, Zhang J, Vangveravong S, Chu W, Li S, Tu Z, Xu J, Mach RH. Functional assays to define agonists and antagonists of the sigma-2 receptor. Anal Biochem. 2014 Mar 1;448:68-74. doi: 10.1016/j.ab.2013.12.008. PubMed PMID: 24333652; PubMed Central PMCID: PMC3923374.
