Cytembena is a novel and potent inhibitor of DNA biosynthesis

Physicochemical Properties

Molecular Weight	307.07262
Exact Mass	305.95
CAS #	21739-91-3
Related CAS #	5711-40-0 (free acid);21739-91-3 (sodium);
PubChem CID	23665583
Appearance	Typically exists as solid at room temperature
Density	1.59g/cm3
Boiling Point	417.9ºC at 760mmHg
Melting Point	260 - 263ºC
Flash Point	206.5ºC
Vapour Pressure	9.92E-08mmHg at 25°C
LogP	0.906
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	17
Complexity	309
Defined Atom Stereocenter Count	0
SMILES	[Na+].COC1C=CC(C(/C(=C\C([O-])=O)/Br)=O)=CC=1
InChi Key	DVDCIQWIGOVWEX-MLBSPLJJSA-M
InChi Code	InChI=1S/C11H9BrO4.Na/c1-16-8-4-2-7(3-5-8)11(15)9(12)6-10(13)14;/h2-6H,1H3,(H,13,14);/q;+1/p-1/b9-6+;
Chemical Name	sodium;(E)-3-bromo-4-(4-methoxyphenyl)-4-oxobut-2-enoate
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
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

ADME/Pharmacokinetics	Absorption, Distribution and Excretion IN NORMAL SUBJECTS RENAL EXCRETION WAS APPROX 7.8% OF GIVEN DOSE IN 15 HR FOLLOWING SINGLE IV INJECTION OF 200 MG. IN PT WITH IMPAIRED RENAL FUNCTION, URINARY EXCRETION WAS LESS & DIRECTLY CORRELATED WITH DECR IN ENDOGENOUS CREATININE CLEARANCE RATE. WHEN (14)C-LABELED CYTEMBENA WAS ADMIN, RATS EXCRETED GREATER THAN 70% & DOGS GREATER THAN 50% OF RADIOACTIVE DOSE IN 24 HR; MOST OF LABEL WAS FOUND IN URINE. KIDNEY RETAINED HIGHEST LEVEL OF RADIOACTIVITY AFTER 24 HR. Metabolism / Metabolites CYTEMBENA WAS DEMETHYLATED BY RABBIT LIVER MICROSOMES & WAS DEBROMINATED & SATURATED BY 100,000-G SUPERNATANT FRACTION IN PRESENCE OF GLUTATHIONE & NADPH. STRUCTURES OF METABOLITES TENTATIVELY IDENTIFIED BY MASS SPECTROMETRY. CYTEMBENA UNDERGOES RAPID REACTION WITH THIOL COMPD INCL GLUTATHIONE & CYSTEINE, RESULTING IN ALKYLATION OF SULFUR. PRODUCT OF CYTEMBENA & GLUTATHIONE WAS ISOLATED & TESTED FOR CYTOTOXICITY; IT WAS LESS EFFECTIVE THAN FREE CYTEMBENA. REACTION MAY BE DETOXIFICATION PROCESS. Biological Half-Life IN 8 SUBJECTS WITH NORMAL RENAL FUNCTION, CYTEMBENA HAD A SERUM HALF-LIFE OF APPROX 13.5 HR.
References	[1]. Phase II trial of cytembena in patients with advanced ovarian and breast cancer. Cancer Treat Rep. 1976 Nov;60(11):1655-8. [2]. Description of a permeable eukaryotic cell system to study agents affecting DNA synthesis: demonstration that cytembena is a direct inhibitor of replicative DNA synthesis. J Natl Cancer Inst. 1977 Apr;58(4):1167-9.
Additional Infomation	Cytembena can cause cancer according to The National Toxicology Program. Cytembena is a white to off-white powder. (NTP, 1992) Cytembena is a cytostatic agent that interferes with DNA synthesis.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.2566 mL	16.2829 mL	32.5659 mL
	5 mM	0.6513 mL	3.2566 mL	6.5132 mL
	10 mM	0.3257 mL	1.6283 mL	3.2566 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.