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

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

Used in Anticancer Applications:
Estramustine is used as an antineoplastic agent for the treatment of various types of cancer. It is particularly effective in the treatment of breast cancer and prostate cancer, where it exhibits its therapeutic effects by binding to the estrogen receptor and inducing DNA cross-linking, leading to cell cycle arrest and apoptosis.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, Estramustine is used as a key component in the development of cancer therapeutics. Its dual mechanism of action makes it a valuable compound for the treatment of hormone-responsive cancers, and ongoing research is focused on optimizing its efficacy and reducing potential side effects.
Used in Drug Delivery Systems:
Similar to gallotannin, Estramustine can also be incorporated into drug delivery systems to enhance its bioavailability, targeting, and therapeutic outcomes. These systems may include nanoparticles, liposomes, or other advanced drug carriers designed to improve the delivery of Estramustine to cancer cells while minimizing damage to healthy tissues.

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.

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.

ANTICANCER AGENTS

The invention generally concerns a method for conjugating an active material to a Pt complex.

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.

Expanding the Arsenal of PtIV Anticancer Agents: Multi-action PtIV Anticancer Agents with Bioactive Ligands Possessing a Hydroxy Functional Group

Most multi-action PtIV prodrugs have bioactive ligands containing carboxylates. This is probably due to the ease of carboxylating the OH axial ligands and because following reduction, the active drug is released. A major challenge is to expand the arsenal of bioactive ligands to include those without carboxylates. We describe a general approach for synthesis of PtIV prodrugs that release drugs with OH groups. We linked the OH groups of gemcitabine (Gem), paclitaxel (Tax), and estramustine (EM) to the PtIV derivative of cisplatin by a carbonate bridge. Following reduction, the axial ligands lost CO2, rapidly generating the active drugs. In contrast, succinate-linked drugs did not readily release the free drugs. The carbonate-bridged ctc-[Pt(NH3)2(PhB)(Gem-Carb)Cl2] was significantly more cytotoxic than the succinate-bridged ctc-[Pt(NH3)2(PhB)(Gem-Suc)Cl2], and more potent and less toxic than gemcitabine, cisplatin, and co-administration of cisplatin and gemcitabine.

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.

Therapeutic use of at least one botulinum neurotoxin in the treatment of pain induced by at least one anti-neoplastic agent

The present invention relates to a method of treating or preventing pain or pains induced by an anti-neoplastic agent, comprising the step of administering an effective amount of at least one botulinum neurotoxin to a patient in need thereof.

Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same

Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.