2998-57-4

Basic information

• Product Name: Estramustine
• Synonyms: LEO 275;1,3,5(10)-Estratriene-3,17β-diol 3-[bis(2-chloroethyl)carbamate];1,3,5(10)-Estratriene-3,17β-diol 3-[N,N-bis(2-chloroethyl)carbamate];Estamustine;3,5(10)-triene-3,17-diol(17beta)-estra-3-(bis(2-chloroethyl)carbamate);estradiol,3-(bis(2-chloroethyl)carbamate);ESTRAMUSTINE;ESTRAMUSTINE SODIUM PHOSPHATE
• CAS NO: 2998-57-4
• Molecular Formula: C23H31Cl2NO3
• Molecular Weight: 440.4
• EINECS: 221-076-3
• Mol File: 2998-57-4.mol
• Article Data: 8

Chemical Properties

• Melting Point: 104-105°
• Boiling Point: 565.751 °C at 760 mmHg
• Flash Point: 295.956 °C
• Appearance: /
• Density: 1.253 g/cm³
• Vapor Pressure: 1.23E-13mmHg at 25°C
• Refractive Index: 1.576
• PKA: 15.05±0.40(Predicted)
• Water Solubility: 1mg/L(30 oC)
• CAS DataBase Reference: Estramustine(CAS DataBase Reference)
• NIST Chemistry Reference: Estramustine(2998-57-4)
• EPA Substance Registry System: Estramustine(2998-57-4)

Safety Data

• Hazardous Substances Data: 2998-57-4(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 2998-57-4 differently. You can refer to the following data:
1. Antineoplastic.
2. Estradiol 3-[N,N-Bis(2-chloroethyl)carbamate] is used treatment of breast cancer. Also used in the treatment of prostate cancer.

Indications

Estramustine phosphate sodium (Emcyt) is a hybrid structure combining estradiol and a nitrogen mustard in a single molecule. The drug has been approved for use in prostatic carcinomas and will produce clinical remissions in one-third of patients who have failed to respond to previous estrogen therapy. The mechanism of action of estramustine is not well defined, but it does not appear to require either alkylation of DNA or the presence of estrogen receptors in tumor cells. Nonetheless, the toxicities of the drug are similar to those of estrogen therapy: breast tenderness and enlargement (gynecomastia), fluid retention, mild nausea, and an increased risk of thrombophlebitis and pulmonary embolism.The drug is not myelosuppressive.

Definition

ChEBI: A carbamate ester obtained by the formal condensation of the hydroxy group of 17beta-estradiol with the carboxy group of bis(2-chloroethyl)carbamic acid.

Biological Functions

Estramustine has a low affinity for the βm tubulin isotype, which often is overexpressed in estramustineresistant prostatic neoplasms as one defense against this therapeutic intervention.

Mechanism of action

Because this anticancer agent contains a carbamylated nitrogen mustard moiety, it is most commonly classified as a DNA alkylator; however, it is now known that its primary mechanism of antineoplastic action is inhibition of mitosis.

InChI:InChI=1/C23H31Cl2NO3/c1-23-9-8-18-17-5-3-16(29-22(28)26(12-10-24)13-11-25)14-15(17)2-4-19(18)20(23)6-7-21(23)27/h3,5,14,18-21,27H,2,4,6-13H2,1H3/t18-,19-,20+,21+,23+/m1/s1

Upstream product

• 2998-56-3 N,N-bis-(2-chloroethyl)carbamoyl chloride 
• 50-28-2 estradiol 
• 62899-40-5 Estromustine 

Downstream Products

• 50-28-2 estradiol 
• 53-16-7 Estrone 

Relevant articles and documents

Comparative study of microtubule inhibitors - Estramustine and natural podophyllotoxin conjugated PAMAM dendrimer on glioma cell proliferation

The synthetic estramustine (EM) and natural podophyllotoxin (PODO) anti-mitotic agents that inhibit tubulin polymerization are known anticancer agents. As low bioavailability limits their anticancer properties, we investigated whether conjugation with PAMAM dendrimer (D) could enhance the activity of D-EM and D-PODO by altering their release pattern. Release kinetics indicated synthesized conjugates to be stable against hydrolytic cleavage and showed sustained release characteristics. However, release of D-EM was slow compared to D-PODO conjugate. Antitumor effect of these conjugates on glioma cells revealed (i) increased cell death and cell cycle arrest (ii) decreased migration and (iii) increased tubulin depolymerization as compared to free drug. Importantly, the effects of natural PODO conjugate on glioma cell survival and migration is more pronounced than D-EM.

2-methoxyestramustine and derivative thereof, and preparation method and application thereof

The invention discloses 2-methoxyestramustine and a derivative thereof. The structural formula of the 2-methoxyestramustine is shown as a formula 1-4. According to the 2-methoxyestramustine disclosedby the invention, 2-methoxyestradiol is used as a carrier, an alkylating agent (nitrogen mustard) is connected through carbamate to form a bifunctional drug molecular compound, the whole molecule is used as an anti-mitotic agent, and after carbamate is metabolized and hydrolyzed in vivo, 2-methoxyestradiol released by metabolite mediation can still continue to play an anti-tumor role. The derivative of the 2-methoxyestradiol can be used as the prodrug of the 2-methoxyestradiol. The invention also discloses a preparation method of the 2-methoxyestramustine and the derivative thereof, the preparation method can be used for preparing the 2-methoxyestramustine and the derivative thereof, and the yield is relatively high. The invention further discloses application of the 2-methoxyestramustineand the derivative thereof in a medicine for treating tumors or multiple myeloma.

THERAPEUTIC FOR HEPATIC CANCER

A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.