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Cyclophosphamide ppt
- 2. CYCLOPHOSPHAMIDE Used in the treatment of WBC cancers (AML/ALL) and Lymphoma Cell Cycle – Non specific Alkylating agent Adds Alkyl group (CnH2n+1) to DNA
- 3. CYCLOPHOSPHAMIDE Mechanism of Action • the main effect of cyclophosphamide is due to its metabolite Phosphoramide mustard • Phosphoramide mustard forms DNA crosslinks between (interstrand crosslinkages) and within (intrastrand crosslinkages) DNA strands at guanine N-7 position, this eventually leads to cell death
- 7. CONCLUSION Expression of genes that code for Cytochrome P450 (Oxidase Enzyme) and ALDH enzymes affects the sensitivity of Cancer cells to Cyclophosphamide since these enzymes affect the metabolism of the prodrug (Cyclophosphamide) to its active Phosphoramide mustard metabolite.
Hinweis der Redaktion
- Cyclophosphamide is a prodrug. It must be metabolized by the body to convert it in its active metabolite.Formation of Cyclophosphamide’s active metabolite occurs mainly in the liver.Phospharamide is the active metabolite that creates crosslinks in the DNA.
- OXIDASE ENZYMES, particularly the CYTOCHROME P450 SYSTEM in the liver convert Cyclophosphamide prodrug to active metabolites.The main active metabolite is 4-HYDROXYCYCLOPHOSPHAMIDE which exists in equilibrium with its tautomer, ALDOPHOSPHAMIDE.Most ALDOPHOSPHAMIDE is then oxidized by the enzyme ALDEHYDE DEHYDROGENASE to make CARBOXYCYCLOPHOSPHAMIDE.A small proportion of ALDOPHOSPHAMIDE freely diffuses into cells and is decomposed into two compounds, PHOSPHORAMIDE MUSTARD and ACROLEIN.