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Target intelligence / Profile preview
Hypoxia-Selective Activation Releasing Bromo-Isophosphoramide Mustard (N/A)
- Target
- N/A
- Molecular classification
- Prodrug, Alkylating Agent (after activation), Chemotherapeutic Agent (after activation)
01
Overview
Hypoxia-Selective Activation Releasing Bromo-Isophosphoramide Mustard describes the mechanism of action of a class of anticancer prodrugs, exemplified by Evofosfamide (TH-302). These prodrugs are designed to be selectively activated in the hypoxic environment of solid tumors, releasing the cytotoxic agent bromo-isophosphoramide mustard (Br-IPM), a DNA alkylator. The 2-nitroimidazole trigger group undergoes bioreduction in low oxygen conditions, leading to the release of the active drug and subsequent cell death primarily within the tumor microenvironment. After activation and release within hypoxic tumor regions, Br-IPM can diffuse into adjacent normoxic tumor cells.
- Other names
- Evofosfamide (TH-302)Bromo-isophosphoramide mustard (Br-IPM)Hypoxia-activated prodrugTumor hypoxia-activated prodrug
02
Mechanism of action
Hypoxia-selective bioreductive activation releasing bromo-isophosphoramide mustard, a DNA cross-linking agent.
03
Biological functions
DNA alkylation (after activation)Cell death induction (after activation)Tumor growth inhibition (after activation)
04
Disease associations
Cancer
05
Safety considerations
Systemic toxicity (related to incomplete selectivity)Development of resistanceOff-target effects of Br-IPM
06
Interacting drugs
Doxorubicin
1 more in the full profile.
07
Biomarkers
Tumor hypoxia levelsExpression of bioreductive enzymes
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