Loading
Drugs that block the enzyme that activates Notch signalling; nirogacestat became the first approved, in 2023, for desmoid tumours, a rare but destructive growth of connective tissue.
Gamma-secretase cleaves Notch receptors to release their active fragment. Inhibitors developed originally for Alzheimer's disease were repurposed for Notch-driven cancers; nirogacestat (Ogsiveo) reduced progression and pain in desmoid tumours in the DeFi trial and was approved by the FDA in 2023. Gamma-secretase inhibition also boosts BCMA on myeloma cells, so it is combined with BCMA-directed CAR-T and bispecifics, and T-cell acute lymphoblastic leukaemia remains a target despite gut toxicity.
Small molecules inhibit the presenilin catalytic site of gamma-secretase, preventing Notch intracellular domain release and Notch target gene transcription.
Nirogacestat is the first approved medicine for desmoid tumours, locally invasive growths that do not spread but can be crippling; it works by blocking Notch signalling.
Query for this technology: (TITLE:"Gamma-secretase inhibitors" OR ABSTRACT:"Gamma-secretase inhibitors") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Gamma-secretase inhibitors, not a curated reading list.
Shares DeFi, Nirogacestat, Sarcomas (soft tissue, bone, GIST).
Shares DeFi, Nirogacestat, Sarcomas (soft tissue, bone, GIST).
Shares A Study of Nirogacestat in Japanese Adults With Desmoid Tumors/Aggressive Fibromatosis (DT/AF), Gamma-secretase (PSEN1), DeFi, Nirogacestat.
Shares Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat in Participants With RRMM, Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Nirogacestat, Pomalidomide, and Dexamethasone in Participants Wi, Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat, Lenalidomide, and Dexamethasone in Participants With RRMM, Multiple myeloma.
Shares Nirogacestat, Multiple myeloma.
Shares A Study of Nirogacestat in Japanese Adults With Desmoid Tumors/Aggressive Fibromatosis (DT/AF), Nirogacestat.