68047-06-3

Basic information

• Product Name: 4-HYDROXYTAMOXIFEN
• Synonyms: trans-4-Hydroxytamoxifen, (Z)-4-(1-[4-(Dimethylaminoethoxy)phenyl]-2-phenyl-1-butenyl)phenol;(Z)-3,4-Diphenyl-4-[4-[2-(dimethylamino)ethoxy]phenyl]-3-buten-1-ol;2-[4-[(E)-1-(4-Hydroxyphenyl)-2-phenyl-1-butenyl]phenoxy]-N,N-dimethylethanamine;4-[(E)-1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-phenyl-1-butenyl]phenol;cis-4-Hydroxytamoxifen;N,N-Dimethyl-2-[4-[(E)-1-(4-hydroxyphenyl)-2-phenyl-1-butenyl]phenoxy]ethanamine;4-(1-(4-(dimethylaminoethoxy)phenyl)-2-phenyl-1-butenyl)phenol;(Z)-4-(1-[4-(Dimethylaminoethoxy)phenyl]-2-phenyl-1-butenyl)phenol
• CAS NO: 68047-06-3
• Molecular Formula: C₂₆H₂₉NO₂
• Molecular Weight: 387.51
• Product Categories: Drug Analogues;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;Aromatics;Metabolites & Impurities
• Mol File: 68047-06-3.mol
• Article Data: 16

Chemical Properties

• Melting Point: 105-107°C
• Boiling Point: 513.45°C (rough estimate)
• Flash Point: 264.9°C
• Appearance: white/powder
• Density: 1.1005 (rough estimate)
• Vapor Pressure: 3.35E-11mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: 2-8°C
• Solubility: 95% ethanol: 20 mg/mL
• PKA: 10.35±0.15(Predicted)
• Stability: Stable. Store cool. Incompatible with strong oxidizing agents.
• CAS DataBase Reference: 4-HYDROXYTAMOXIFEN(CAS DataBase Reference)
• NIST Chemistry Reference: 4-HYDROXYTAMOXIFEN(68047-06-3)
• EPA Substance Registry System: 4-HYDROXYTAMOXIFEN(68047-06-3)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-63
• Safety Statements: 22-23-36
• WGK Germany: 3
• RTECS: SL1210000
• Hazardous Substances Data: 68047-06-3(Hazardous Substances Data)

Usage

Description

4-Hydroxytamoxifen, a hydroxylated analogue of tamoxifen, is a metabolite of tamoxifen with anti-estrogenic properties. It plays a significant role in the therapeutic effects of tamoxifen, a selective estrogen receptor modulator used in the treatment of breast cancer.
Used in Pharmaceutical Industry:
4-Hydroxytamoxifen is used as an active metabolite for the treatment of breast cancer. It exhibits anti-estrogenic properties, which help in blocking the effects of estrogen, a hormone that promotes the growth of breast cancer cells. Its role in tamoxifen's therapeutic effects makes it a crucial component in the management of hormone receptor-positive breast cancer.
Used in Research Applications:
4-Hydroxytamoxifen is used as a research tool for studying the mechanisms of action of tamoxifen and its effects on estrogen receptor-positive breast cancer cells. It aids in understanding the anti-estrogenic properties and the role of metabolites in the therapeutic efficacy of tamoxifen.
Used in Drug Development:
4-Hydroxytamoxifen serves as a starting point for the development of new drugs with improved anti-estrogenic properties and fewer side effects. Its structural and functional characteristics provide valuable insights for the design and synthesis of novel compounds targeting estrogen receptor-positive breast cancer.

Biological Activity

estrogen receptors (er) are members of the superfamily of ligand-modulated nuclear receptors that mediate the actions of steroid hormones, vitamin d, retinoids, and thyroid hormones. er is activated in vivo when bound by naturally occurring estrogens such as 17α-estradiol. in addition to regulating these physiological processes, estrogen also plays a central role in stimulating breast cancer growth. (z)-tamoxifen is a first generation selective er modulators that is currently approved by the fda and is widely used to treat estrogen-dependent breast cancers. its active metabolite, (z)-4-hydroxytamoxifen, is a potent estrogen receptor modulator.

Biochem/physiol Actions

Cell permeable: yes

in vitro

(z)-4-hydroxytamoxifen binds to er with 8-fold higher affinity than tamoxifen. it was found that only the z isomer has the required antiestrogenic activity; the (e)-4-hydroxytamoxifen has only about 5% of its affinity for the er [1].

in vivo

the antioestrogenic activities of (z)-4-hydroxytamoxifen and tamoxifen were determined after oral administration. (z)-4-hydroxytamoxifen was administered to groups of immature rats which also received s.c. injections of 0-2 μg oestradiol. both compounds produced a dose-related decrease in uterine wet weight when compared with the oestradiol-treated controls. at a dose of 1 μg/day, the antiuterotrophic effects of (z)-4-hydroxytamoxifen and tamoxifen were not significantly different but at 5μg/day, (z)-4-hydroxytamoxifen was more active (p < 0.01). (z)-4-hydroxytamoxifen therefore appears to retain its potent antioestrogenic activity after oral administration [2].

references

[1] donna d. yu and barry m. forman. simple and efficient production of (z)-4-hydroxytamoxifen, a potent estrogen receptor modulator. j. org. chem. 2003, 68, 9489-9491[2] jordan vc, collins mm, rowsby l, prestwich g. a monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. j endocrinol. 1977 nov;75(2):305-16.

InChI:InChI=1/C26H29NO2/c1-4-25(20-10-14-23(28)15-11-20)26(21-8-6-5-7-9-21)22-12-16-24(17-13-22)29-19-18-27(2)3/h5-17,28H,4,18-19H2,1-3H3/b26-25-

Upstream product

• 185223-78-3 (E,Z)-1-[4-(benzyloxy)phenyl]-1-(4-hydroxyphenyl)-2-phenylbut-1-ene 
• 108-95-2 phenol 
• 622-86-6 2-chloroethoxybenzene 
• 96212-84-9 (E)-1-bromo-2-phenyl-1-(trimethylsilyl)-1-butene 
• 126402-33-3 1-bromo-1-(4-<(2-tetrahydropyranyl)oxy>phenyl)-2-phenyl-1-butene 
• 611-99-4 4,4'-Dihydroxybenzophenone 
• 93-55-0 1-phenyl-propan-1-one 
• 91221-46-4 1,1-bis(4-hydroxyphenyl)-2-phenyl-1-butene 
• 107-99-3 2-(dimethylamino)ethyl chloride 
• 10540-29-1 tamoxifen 
• 75-03-6 ethyl iodide 
• 93790-54-6 [2-(4-iodophenoxy)ethyl]dimethylamine 
• 2633-75-2 ethylzinc chloride 
• 106-41-2 4-bromo-phenol 

Downstream Products

• 1454890-27-7 4-((E)-1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenyl 4-(-2-((4-methoxy-1H,1'H-[2,2'-bipyrrol]-5-yl)methylene)-3,5-dimethyl-2H-pyrrol-4-yl)-4-oxobutanoate 
• 1454890-28-8 4-((E)-1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-enyl)phenyl 10-((Z)-2-((4-methoxy-1H,1'H-2,2'-bipyrrol-5-yl)methylene)-3,5-dimethyl-2H-pyrrol-4-yl)-10-oxodecanoate 
• 174592-47-3 trans 4-hydroxytamoxifen 
• 76117-70-9 (E)-4-{1-[4-(2-dimethylaminoethoxy)phenyl]-2-phenylbut-1-enyl}phenyl acetate 
• 199541-66-7 4-hydroxytamoxifen quinone methide 

Relevant articles and documents

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method development for screening of potential tamoxifen-drug/herb interaction via in vitro cytochrome P450 inhibition assay

Screening for potential drug-drug interaction (DDI) or herb-drug interaction (HDI) using in vitro cytochrome P450 inhibition (IVCI) assays requires robust analytical methods with high sensitivity and reproducibility. Utilization of liquid chromatography-mass spectrometry (LC-MS) for analyte quantification is often hampered by the presence of non-volatile IVCI sample buffer constituents that often results in ion suppression. In this study, to enable screening of drug interactions involving tamoxifen (TAM) metabolism using IVCI-LC-MS/MS, a liquid–liquid extraction (LLE) method was developed and optimized for sample clean-up. Utilization of chloroform as extraction solvent and adjustment of sample pH to 11 was found to result in satisfactory recovery (>70%) and low ion suppression (A LC-MS/MS method was subsequently developed and validated for simultaneous quantification of major TAM metabolites, such as N-desmethyltamoxifen (NDT), endoxifen (EDF) and 4-hydroxytamoxifen (HTF) to enable IVCI sample analysis. Satisfactory separation of E-/Z-isomers of endoxifen with peak resolution (Rs) of 1.9 was achieved. Accuracy and precision of the method was verified within the linear range of 0–50 ng/mL for NDT, 0–25 ng/mL for HTF and 0–25 ng/mL for EDF (E/Z isomers). Inhibitory potency (IC50, Ki and mode of inhibition) of known CYP inhibitors and Strobilanthes crispus extract was then evaluated using the validated method. In summary, the results demonstrated applicability of the developed LLE and validated LC-MS/MS method for in vitro screening of DDI and HDI involving TAM metabolism.

Methods for Determining the Oncogenic Condition of Cell, Uses Thereof, and Methods for Treating Cancer

The invention relates to methods for detecting the oncogenic condition of cells, including step where the amount of the OCDO compound in said cells is measured, and to the uses thereof. The invention further relates to OCDO inhibitors for use in methods for treating cancer.

METHODS FOR DETERMINING THE ONCOGENIC CONDITION OF CELL, USES THEREOF, AND METHODS FOR TREATING CANCER

The invention relates to methods for detecting the oncogenic condition of cells, including step where the amount of the OCDO compound in said cells is measured, and to the uses thereof. The invention further relates to OCDO inhibitors for use in methods for treating cancer