Sardomozide HCl (formerly known as SAM486A; CGP48664), the hydrochloride salt of sardomozide, is a novel, potent and 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.

Physicochemical Properties

Molecular Formula	C11H16CL2N6
Molecular Weight	230.26906
Exact Mass	302.081
CAS #	138794-73-7
Related CAS #	Sardomozide;149400-88-4
PubChem CID	10402702
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Boiling Point	490.6±55.0 °C at 760 mmHg
Flash Point	250.5±31.5 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.768
LogP	-0.49
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	19
Complexity	368
Defined Atom Stereocenter Count	0
SMILES	C1C/C(=N\N=C(N)N)/C2=C1C(=CC=C2)C(=N)N.Cl.Cl
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+
Chemical Name	(E)-2-(4-carbamimidoyl-2,3-dihydro-1H-inden-1-ylidene)hydrazinecarboximidamide dihydrochloride
Synonyms	CGP 48664 SAM-486ACGP-48664 SAM486A CGP48664 SAM 486A
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	IC50: 5 nM (SAMDC)[1]
ln Vitro	An IC50 of 5 nM was observed in a cell experiment for the S-adenosylmethionine decarboxylase (SAMDC) inhibitor sardomozide. After being treated with 3 μM Sardomozide for 48 hours, intracellular SAMDC activity drops to 10% of the control level[1]. Vacuole production is not seen in CHO/664 cells grown in the presence of Sardomozide and treated with DENSPM; instead, the cells exhibit growth inhibition and DENSPM levels comparable to those of the original CHO cells[2].
Cell Assay	The parent CHO cell line is chronically exposed to increasing levels of Sardomozide for at least eight passages beginning at 0.1 μM. Cell lines are serially exposed to increasing concentrations until a panel of sublines is obtained resistant to 1 (CHO/1). 3 (CHO/3), 10 (CHO/10), 30 (CHO/30), and 100 (CHO/100) μM Sardomozide for comparative studies[2].
References	[1]. CGP 48664, a new S-adenosylmethionine decarboxylase inhibitor with broad spectrum antiproliferative and antitumor activity. Cancer Res. 1994 Jun 15;54(12):3210-7. [2]. Lysosomal sequestration of polyamine analogues in Chinese hamster ovary cells resistant to the S-adenosylmethionine decarboxylase inhibitor, CGP-48664. Cancer Res. 1998 Sep 1;58(17):3883-90.

Solubility Data

Solubility (In Vitro)

DMSO : ~10 mg/mL (~32.98 mM) H2O : ~3.85 mg/mL (~12.70 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 1 mg/mL (3.30 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.3427 mL	21.7136 mL	43.4273 mL
	5 mM	0.8685 mL	4.3427 mL	8.6855 mL
	10 mM	0.4343 mL	2.1714 mL	4.3427 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.