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laromustine
- Development stage
- Phase 3
- Lead developer
- Vion Pharmaceuticals
- Modality
- Metabolically Activated Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules
- Administration
- Intravenous
01
Overview
Laromustine is a small molecule sulfonyl hydrazine prodrug with antineoplastic activity, developed primarily for the treatment of hematologic malignancies such as acute myeloid leukemia (AML), myelodysplastic syndromes, and other cancers including glioma and lymphoma. Upon administration, laromustine is activated in the bloodstream to release the DNA chloroethylating agent 90CE, which preferentially alkylates the O6 position of guanine in DNA. This results in interstrand DNA cross-links, strand breaks, chromosomal aberrations, and disruption of DNA synthesis. Additionally, intracellular metabolism releases methyl isocyanate that inhibits O6-methylguanine-DNA methyltransferase (MGMT), an enzyme involved in DNA repair. Laromustine has demonstrated significant antileukemia activity and was investigated up to phase III clinical trials but development was ultimately suspended or discontinued for all major indications[2][3][4][5][6].
- Brand names
- Onrigin
- Other names
- laromustineCloretazineOnrigin173424-77-6
02
Targets
POLB (DNA polymerase beta)AGT (O6-methylguanine-DNA methyltransferase)
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