N-Desmethyltamoxifen is the major metabolite of Tamoxifen in the human body. N-Desmethyltamoxifen, a weaker anti-estrogen, is a protein kinase C (PKC) inhibitor ten times more potent than Tamoxifen. N-Desmethyltamoxifen is also an effective regulator of ceramide metabolism in human AML cells, limiting ceramide glycosylation, hydrolysis and sphingosine phosphorylation.

Physicochemical Properties

Molecular Formula	C25H27NO
Molecular Weight	357.5
Exact Mass	357.209
CAS #	31750-48-8
Related CAS #	N-Desmethyltamoxifen hydrochloride;15917-65-4
PubChem CID	6378383
Appearance	Typically exists as solid at room temperature
Density	1.047 g/cm3
Boiling Point	485.8ºC at 760 mmHg
Flash Point	213.2ºC
LogP	6.044
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	8
Heavy Atom Count	27
Complexity	437
Defined Atom Stereocenter Count	0
SMILES	C1(/C(/C2C=CC(OCCNC)=CC=2)=C(\C2C=CC=CC=2)/CC)C=CC=CC=1
InChi Key	NYDCDZSEEAUOHN-IZHYLOQSSA-N
InChi Code	InChI=1S/C25H27NO/c1-3-24(20-10-6-4-7-11-20)25(21-12-8-5-9-13-21)22-14-16-23(17-15-22)27-19-18-26-2/h4-17,26H,3,18-19H2,1-2H3/b25-24-
Chemical Name	2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]-N-methylethanamine
Synonyms	ICI-55548 Desmethyltamoxifen N-Desmethyltamoxifen
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

ln Vitro	Over a 48-hour period, N-Desmethyltamoxifen (20-500 ng/ml) significantly suppresses the functions of all seven glioma cell lines (T98G, U87, U138, U373, ALW, AUK, and CAS cells). The MCF 7 human breast cancer cells are inhibited in their ability to proliferate by N-desmethyltamoxifen (1.5-10 μM; 114 hours) [2]. The principal quantitative metabolite of tamoxifen, N-desmethyltamoxifen, is generated through CYP3A4/5-mediated tamoxifen catalysis [3].
Cell Assay	Cell viability assay [2] Cell Types: MCF 7 human breast cancer cells Tested Concentrations: 1.5, 2.5, 5, 7.5, 10 μM Incubation Duration: 114 hrs (hours) Experimental Results: Inhibition of the growth of MCF 7 human breast cancer cells
ADME/Pharmacokinetics	Metabolism / Metabolites N-Desmethyltamoxifen has known human metabolites that include N-Desdimethyltamoxifen, alpha-hydroxy-N-desmethyltamoxifen, and Endoxifen. N-Desmethyltamoxifen is a known human metabolite of tamoxifen.
References	[1]. A comparison of the relative chemosensitivity of human gliomas to tamoxifen and n-desmethyltamoxifen in vitro. J Neurooncol. 1994;19(2):97-103. [2]. Modification of sphingolipid metabolism by tamoxifen and N-desmethyltamoxifen in acute myelogenous leukemia--Impact on enzyme activity and response to cytotoxics. Biochim Biophys Acta. 2015 Jul;1851(7):919-28. [3]. N-desmethyltamoxifen inhibits growth of MCF 7 human mammary carcinoma cells in vitro. Eur J Cancer Clin Oncol. 1983 Aug;19(8):1179-81. [4]. Use of Antidepressants in Patients with Breast Cancer Taking Tamoxifen. J Breast Cancer. 2010 Dec;13(4):325-336.
Additional Infomation	N-Desmethyltamoxifen is a stilbenoid. N-Desmethyltamoxifen is a main metabolite of the selective estrogen receptor modulator tamoxifen with anti-estrogen activity. N-desmethyltamoxifen blocks estrogen from binding to the estrogen receptor. This may inhibit estrogen-associated signaling and tumor growth in estrogen-positive tumor cells. Conversion of N-desmethyltamoxifen from tamoxifen is catalyzed by cytochrome P-450 enzymes 3A4 and 3A5. N-desmethyltamoxifen is further hydroxylated, mainly by CYP2D6, to endoxifen, the major clinically active metabolite of tamoxifen.

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	2.7972 mL	13.9860 mL	27.9720 mL
	5 mM	0.5594 mL	2.7972 mL	5.5944 mL
	10 mM	0.2797 mL	1.3986 mL	2.7972 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.