Onrigin (laromustine) / Vion - LARVOL DELTA

Targeting the repair of DNA-protein crosslinks induced by bifunctional alkylating agents (AACR 2024) - "Micromolar concentrations of the nitrogen mustard mechlorethamine and nitrosourea lomustine induced significant DPC formation while more modest DPC formation was observed using similar concentrations of the chloroethylating agents carmustine and laromustine, as well as cisplatin. Chemotherapeutic sensitization by targeting SPRTN could suggest a therapeutic strategy to improve effectiveness of several DNA-targeted anticancer agents, especially if extended to other therapeutics that trap DPCs such as inhibitors of topoisomerase and poly(ADP-ribose) polymerase. Further, identifying structure-function relationships with respect to bifunctional alkylating agents and DPC formation could inform the future development and clinical utilization of these chemotherapies."

Hematological Malignancies • Leukemia • Oncology

[VIRTUAL] Quantifying DNA-protein crosslinks induced by bifunctional alkylating agents in cultured human leukemia cells (AACR-II 2020) - "Bifunctional alkylating agents, such as cisplatin and several nitrosoureas, have clinical utility as antineoplastic drugs largely due to their DNA alkylating and crosslinking activity. Other drug candidates such as laromustine (VNP-40101M) and dianhydrogalacticol (VAL-083) have similar DNA-alkylating activities and have shown success in clinical trials against hard-to-treat cancers such as acute myelogenous leukemia and glioblastoma multiforme...The nitrogen mustard mechlorethamine and the chloroethyl nitrosoureas carmustine and lomustine were the most potent agents, yielding significant DPC formation at clinically relevant doses (10-5 M)...Dianyhydrogalacticol, epichlorohydrin, and diepoxybutane, which all rely on epoxide functional groups for attachment to cellular nucleophiles, required at least an order of magnitude higher drug concentrations for significant DPC observation. These data suggest bifunctional alkylating agents featuring halide leaving groups are most..."

Preclinical • Acute Myelogenous Leukemia • Brain Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Oncology