Agerafenib

{
  "id": "MLC-T-ONC-009729",
  "term": "Agerafenib",
  "field": "Oncology and biomedicine",
  "definition": "1. An orally bioavailable selective multikinase inhibitor of mutant forms, fusions and rearrangements involving the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET) as well as the serine/threonine-protein kinase B-raf (BRAF), with potential antineoplastic activity. Upon oral administration,agerafenib selectively and potently binds to and targets various RET- and BRAF-containing mutants, fusions and rearrangements. This results in inhibition of cell growth in tumors cells that exhibit increased RET and BRAF activity. RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types; dysregulation of RET activity plays a key role in the development and progression of these cancers. BRAF, a member of the raf family of serine/threonine protein kinases, plays a role in the regulation of MAP kinase/ERK signaling pathways, which may be constitutively activated in certain cancer cells with activating BRAF gene mutations.\n\n2. An orally available v-raf murine sarcoma viral oncogene homolog B1 (B-raf) serine/threonine protein kinase inhibitor with potential antineoplastic activity. Agerafenib specifically and selectively inhibits the activity of the mutated form (V600E) of B-raf kinase. This inhibits the activation of the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway and may result in a decrease in the proliferation of tumor cells expressing the mutated B-raf gene. The Raf mutation BRAF V600E, in which valine is substituted for glutamic acid at residue 600, is frequently found in a variety of human tumors and results in the constitutive activation of the RAF/MEK/ERK signaling pathway that regulates cellular proliferation and survival.",
  "references": [
    "National Cancer Institute Thesaurus"
  ],
  "url": "https://mlchart.com/terminology/oncology/agerafenib/"
}