Этопозидфосфат

Description

Etoposide phosphate is a water-soluble prodrug of the anticancer drug etoposide, containing a phosphate group in the 4' position of the E-ring of the molecule. English name Etoposide phosphate, chemical formula C29H33O16P, CAS number 117091-64-2, EC number 630-364-1, DSSTox ID DTXSID9048645. Also known under the development code BMY 40481 and the trade name Etopophos.

Mechanism of action

After intravenous administration, it is quickly dephosphorylated in the blood plasma to the active substance - etoposide, an inhibitor of topoisomerase II, an enzyme necessary for DNA unwinding and replication. By stabilizing the DNA-topoisomerase II transition complex, etoposide causes double-stranded DNA breaks, which leads to cell cycle arrest in the G2/M phase and apoptosis of tumor cells. The presence of a phosphate group increases the solubility and bioavailability of the compound compared to the parent etoposide, allowing the drug to be administered intravenously with less risk of local irritation.

Basic Attributes

• CAS No: 117091-64-2
• Chemical Formula: C29H33O16P
• Molecular weight: 668.54
• Exact weight: 668.54
• EU number: 630-364-1
• DSSTox ID: DTXSID9048645
• PSA specifications: 207 Å2

Physico-chemical characteristics

• Density: 1?±0.1 g/cm3 (value partially damaged in source)
• Boiling point: 907.7±75.0 °C (predicted value)
• pKa: 1.13±0.50

Scope of application

Used in chemotherapy as part of combined treatment regimens for small cell lung cancer, testicular cancer, lymphomas and leukemia. The water-soluble form allows the drug to be administered intravenously with a smaller volume of solvent.

Advantages of the dosage form

Classic etoposide is poorly soluble in water and requires the use of organic cosolvents (polysorbate, polyethylene glycol, ethanol), which can cause hypotension and anaphylactoid reactions when administered rapidly intravenously. The phosphate form eliminates the need for such cosolvents, allowing the drug to be administered in a smaller volume and in a shorter infusion time, as well as the preparation of solutions of higher concentrations, which simplifies clinical use in the hospital setting.

Storage and transportation conditions

Store in an airtight container, protected from light and moisture, under the conditions provided for pharmaceutical substances with antitumor effects. Requires handling in compliance with personnel protection measures typical for cytotoxic drugs.

Related compounds

Along with etoposide, teniposide is another semi-synthetic derivative of podophyllotoxin with the same mechanism of action; Phosphate prodrugs of this type are also used for other poorly soluble cytostatics, increasing the convenience of infusion administration.

Substance class

A semisynthetic derivative of podophyllotoxin, a plant lignan isolated from the rhizomes of thyroid podophyllum (Podophyllum peltatum) and its Asian relatives, which served as the structural basis for the creation of a number of antitumor drugs with this mechanism of action.