Sardomozide HCl

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

Description:Sardomozide HCl, also known as SAM486A or CGP48664, is a second-generation polyamine synthesis inhibitor, which inhibits the activity of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC). SAM486 is more potent and specific than the first-generation SAMDC inhibitor methylglyoxal (bis) guanylhydrazone (MGBG). Preclinical testing confirmed promising antiproliferative activity. The in vitro tests showed that p53 wild-type NB cells were highly sensitive to SAM486A treatment. Most notably, SAM486A treatment resulted in the rapid accumulation of proapoptotic proteins p53 and Mdm2.

Price and Availability

Sardomozide HCl, purity > 98%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200411Name: Sardomozide HClCAS#: 138794-73-7 (HCl)Chemical Formula: C11H16Cl2N6Exact Mass: Molecular Weight: 303.19Elemental Analysis: C, 43.58; H, 5.32; Cl, 23.38; N, 27.72

Related CAS #:138794-73-7 (HCl)149400-88-4 (free base)

Synonym:CGP 48664; CGP-48664; CGP48664; SAM 486A; SAM-486A; SAM486A; Sardomozide.

IUPAC/Chemical Name:(E)-2-(4-carbamimidoyl-2,3-dihydro-1H-inden-1-ylidene)hydrazinecarboximidamide dihydrochloride

InChi Key:UHEIPGJSFDAPIC-NENXIMLWSA-N

InChi Code:InChI=1S/C11H14N6.2ClH/c12-10(13)8-3-1-2-7-6(8)4-5-9(7)16-17-11(14)15;;/h1-3H,4-5H2,(H3,12,13)(H4,14,15,17);2*1H/b16-9+;;

SMILES Code:NC(C1=CC=CC2=C1CC/C2=NNC(N)=N)=N.[H]Cl.[H]Cl

Technical Data

Additional Information

In a Phase II clinical trial in patients with  metastatic melanoma. Using the present dose and schedule of administration, SAM486A does not have significant therapeutic potential in patients with metastatic melanoma. ( Invest New Drugs. 2005 Jun;23(3):253-6.)  

References

1: Koomoa DL, Borsics T, Feith DJ, Coleman CC,Wallick CJ, Gamper I, Pegg AE, Bachmann AS. Inhibition of S-adenosylmethioninedecarboxylase by inhibitor SAM486A connects polyamine metabolism withp53-Mdm2-Akt/protein kinase B regulation and apoptosis in neuroblastoma.Mol Cancer Ther. 2009 Jul;8(7):2067-75. doi:10.1158/1535-7163.MCT-08-1217. Epub 2009 Jul 7. PubMed PMID: 19584241;PubMed Central PMCID: PMC2731875.

2: Millward MJ, Joshua A, Kefford R, Aamdal S, Thomson D, Hersey P,Toner G, Lynch K. Multi-centre Phase II trial of the polyamine synthesisinhibitor SAM486A (CGP48664) in patients with metastatic melanoma.Invest New Drugs. 2005 Jun;23(3):253-6. PubMed PMID: 15868382.

3: Hu X, Washington S, Verderame MF, Demers LM, Mauger D, Manni A.Biological activity of the S-adenosylmethionine decarboxylase inhibitorSAM486A in human breast cancer cells in vitro and in vivo. Int J Oncol.2004 Dec;25(6):1831-8. PubMed PMID: 15547724.

4: van Zuylen L, Bridgewater J, Sparreboom A, Eskens FA, de Bruijn P,Sklenar I, Planting AS, Choi L, Bootle D, Mueller C, Ledermann JA,Verweij J. Phase I and pharmacokinetic study of the polyamine synthesisinhibitor SAM486A in combination with 5-fluorouracil/leucovorin inmetastatic colorectal cancer. Clin Cancer Res. 2004 Mar15;10(6):1949-55. PubMed PMID: 15041711.

5: Pless M, Belhadj K, Menssen HD, Kern W, Coiffier B, Wolf J, HerrmannR, Thiel E, Bootle D, Sklenar I, Müller C, Choi L, Porter C, CapdevilleR. Clinical efficacy, tolerability, and safety of SAM486A, a novelpolyamine biosynthesis inhibitor, in patients with relapsed orrefractory non-Hodgkin"s lymphoma: results from a phase II multicenterstudy. Clin Cancer Res. 2004 Feb 15;10(4):1299-305. PubMed PMID:14977828.

6: Siu LL, Rowinsky EK, Hammond LA, Weiss GR, Hidalgo M, Clark GM,Moczygemba J, Choi L, Linnartz R, Barbet NC, Sklenar IT, Capdeville R,Gan G, Porter CW, Von Hoff DD, Eckhardt SG. A phase I andpharmacokinetic study of SAM486A, a novel polyamine biosynthesisinhibitor, administered on a daily-times-five every-three-week schedulein patients with Advanced solid malignancies. Clin Cancer Res. 2002Jul;8(7):2157-66. PubMed PMID: 12114416.

7: Kern W, Schleyer E, Bergmann M, Gschaidmeier H, Ehninger G, HiddemannW, Braess J. Detection and separation of the S-adenosylmethionine-decarboxylaseinhibitor SAM486A in human plasma and urine by reversed-phaseion-pairing high-performance liquid chromatography. J Pharmacol ToxicolMethods. 2001 May-Jun;45(3):175-80. PubMed PMID: 11755379.

8: Paridaens R, Uges DR, Barbet N, Choi L, Seeghers M, van der Graaf WT,Groen HJ, Dumez H, Buuren IV, Muskiet F, Capdeville R, Oosterom AT, deVries EG. A phase I study of a new polyamine biosynthesis inhibitor,SAM486A, in cancer patients with solid tumours. Br J Cancer. 2000Sep;83(5):594-601. PubMed PMID: 10944598; PubMed Central PMCID:PMC2363502.

9: Zhou H, Choi L, Lau H, Bruntsch U, Vries EE, Eckhardt G, Oosterom AT,Verweij J, Schran H, Barbet N, Linnartz R, Capdeville R. Populationpharmacokinetics/toxicodynamics (PK/TD) relationship of SAM486A in phaseI studies in patients with advanced cancers. J Clin Pharmacol. 2000Mar;40(3):275-83. PubMed PMID: 10709156.