prodrug PARP inhibitor TSL-1502

{
  "id": "MLC-T-ONC-016238",
  "term": "prodrug PARP inhibitor TSL-1502",
  "field": "Oncology and biomedicine",
  "definition": "An orally bioavailable glucuronide prodrug of TSL-1502M, an inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP), with potential chemo/radiosensitizing and antineoplastic activities. Upon oral administration, prodrug PARP inhibitor TSL-1502 is selectively converted by the enzyme beta-glucuronidase in the tumor microenvironment (TME) to its active form TSL-1502M. TSL-1502M selectively targets and binds to PARP and prevents PARP-mediated DNA repair of DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks and promotes genomic instability and eventually leads to G2/M arrest and apoptosis. This may enhance the cytotoxicity of DNA-damaging agents. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by DNA breaks. The PARP-mediated repair pathway is dysregulated in a variety of cancer cell types. Beta-glucuronidase accumulates in the TME upon release from necrotic tumor cells and certain inflammatory cells.",
  "synonyms": [
    "glucuronide prodrug TSL-1502",
    "PARP inhibitor prodrug TSL-1502"
  ],
  "references": [
    "National Cancer Institute Thesaurus"
  ],
  "url": "https://mlchart.com/terminology/oncology/prodrug-parp-inhibitor-tsl-1502/"
}