WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H200411
CAS#: 138794-73-7 (HCl)
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.
Hodoodo Cat#: H200411
Name: Sardomozide HCl
CAS#: 138794-73-7 (HCl)
Chemical Formula: C11H16Cl2N6
Exact Mass: 0.00
Molecular Weight: 303.190
Elemental 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=N\NC(N)=N)=N.[H]Cl.[H]Cl
Appearance: White to off white 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 water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in water
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: 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.)
| Biological target: | Sardomozide dihydrochloride is an S-adenosylmethionine decarboxylase (SAMDC) inhibitor with an IC50 of 5 nM. |
| In vitro activity: | The antitumor activity of the S-adenosylmethionine decarboxylase (SAMDC) inhibitor SAM486A in human breast cancer cells was investigated. The effects of SAM486A on the proliferation, clonogenicity, invasiveness, cell signaling and PA levels of hormone-independent MDA-MB-435 human breast cancer cells were tested. SAM486A suppressed anchorage-independent and -dependent growth and invasiveness of breast cancer cells, and the inhibition of cell growth was associated with suppression of spermine synthesis. SAM486A increased phosphorylation of STAT-1, -3, ERK1/2 and p38, thus indicating activation of both STAT signaling and the MAPK pathway. The role of activation of STAT signaling and the MAPK pathway in the antitumor action of SAM486A remains to be determined. Reference: Int J Oncol. 2004 Dec;25(6):1831-8. https://www.spandidos-publications.com/ijo/25/6/1831 |
| In vivo activity: | The antitumor action, effects on polyamine pools and tolerability of SAM486A administered to nude mice carrying MDA-MB-435 xenografts were investigated. SAM486A (1 mg/kg) significantly suppressed the growth and spermine levels of established MDA-MB435 breast tumors in nude mice. Inhibition of cellular spermine is consistently observed with SAM486A treatment and may mediate its antitumor action. Reference: Int J Oncol. 2004 Dec;25(6):1831-8. https://www.spandidos-publications.com/ijo/25/6/1831 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 25.0 | 82.46 |
The following data is based on the product molecular weight 303.19 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: | 1. Blavid R, Kusch P, Hauber J, Eschweiler U, Sarite SR, Specht S, Deininger S, Hoerauf A, Kaiser A. Down-regulation of hypusine biosynthesis in Plasmodium by inhibition of S-adenosyl-methionine-decarboxylase. Amino Acids. 2010 Feb;38(2):461-9. doi: 10.1007/s00726-009-0405-x. Epub 2009 Dec 1. PMID: 19949824. 2. Hu X, Washington S, Verderame MF, Demers LM, Mauger D, Manni A. Biological activity of the S-adenosylmethionine decarboxylase inhibitor SAM486A in human breast cancer cells in vitro and in vivo. Int J Oncol. 2004 Dec;25(6):1831-8. PMID: 15547724. |
| In vitro protocol: | 1. Blavid R, Kusch P, Hauber J, Eschweiler U, Sarite SR, Specht S, Deininger S, Hoerauf A, Kaiser A. Down-regulation of hypusine biosynthesis in Plasmodium by inhibition of S-adenosyl-methionine-decarboxylase. Amino Acids. 2010 Feb;38(2):461-9. doi: 10.1007/s00726-009-0405-x. Epub 2009 Dec 1. PMID: 19949824. |
| In vivo protocol: | 1. Hu X, Washington S, Verderame MF, Demers LM, Mauger D, Manni A. Biological activity of the S-adenosylmethionine decarboxylase inhibitor SAM486A in human breast cancer cells in vitro and in vivo. Int J Oncol. 2004 Dec;25(6):1831-8. PMID: 15547724. |
1: Koomoa DL, Borsics T, Feith DJ, Coleman CC, Wallick CJ, Gamper I, Pegg AE, Bachmann AS. Inhibition of S-adenosylmethionine decarboxylase by inhibitor SAM486A connects polyamine metabolism with p53-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 synthesis inhibitor 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 inhibitor SAM486A 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 synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer. Clin Cancer Res. 2004 Mar 15;10(6):1949-55. PubMed PMID: 15041711.
5: Pless M, Belhadj K, Menssen HD, Kern W, Coiffier B, Wolf J, Herrmann R, Thiel E, Bootle D, Sklenar I, Müller C, Choi L, Porter C, Capdeville R. Clinical efficacy, tolerability, and safety of SAM486A, a novel polyamine biosynthesis inhibitor, in patients with relapsed or refractory non-Hodgkin's lymphoma: results from a phase II multicenter study. 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 and pharmacokinetic study of SAM486A, a novel polyamine biosynthesis inhibitor, administered on a daily-times-five every-three-week schedule in patients with Advanced solid malignancies. Clin Cancer Res. 2002 Jul;8(7):2157-66. PubMed PMID: 12114416.
7: Kern W, Schleyer E, Bergmann M, Gschaidmeier H, Ehninger G, Hiddemann W, Braess J. Detection and separation of the S-adenosylmethionine-decarboxylase inhibitor SAM486A in human plasma and urine by reversed-phase ion-pairing high-performance liquid chromatography. J Pharmacol Toxicol Methods. 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, de Vries EG. A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours. Br J Cancer. 2000 Sep;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. Population pharmacokinetics/toxicodynamics (PK/TD) relationship of SAM486A in phase I studies in patients with advanced cancers. J Clin Pharmacol. 2000 Mar;40(3):275-83. PubMed PMID: 10709156.
1. Golbourn BJ, Halbert ME, Halligan K, Varadharajan S, Krug B, Mbah NE, Kabir N, Stanton AJ, Locke AL, Casillo SM, Zhao Y, Sanders LM, Cheney A, Mullett SJ, Chen A, Wassell M, Andren A, Perez J, Jane EP, Premkumar DRD, Koncar RF, Mirhadi S, McCarl LH, Chang YF, Wu YL, Gatesman TA, Cruz AF, Zapotocky M, Hu B, Kohanbash G, Wang X, Vartanian A, Moran MF, Lieberman F, Amankulor NM, Wendell SG, Vaske OM, Panigrahy A, Felker J, Bertrand KC, Kleinman CL, Rich JN, Friedlander RM, Broniscer A, Lyssiotis C, Jabado N, Pollack IF, Mack SC, Agnihotri S. Loss of MAT2A compromises methionine metabolism and represents a vulnerability in H3K27M mutant glioma by modulating the epigenome. Nat Cancer. 2022 Apr 14. doi: 10.1038/s43018-022-00348-3. Epub ahead of print. PMID: 35422502.
