NCIt definition : An orally bioavailable, gamma secretase (GS) and pan-Notch inhibitor, with potential
antineoplastic activity. Upon administration, varegacestat binds to GS and blocks
the proteolytic cleavage and release of the Notch intracellular domain (NICD), which
would normally follow ligand binding to the extracellular domain of the Notch receptor.
This prevents both the subsequent translocation of NICD to the nucleus to form a transcription
factor complex and the expression of Notch-regulated genes. This results in the induction
of apoptosis and the inhibition of growth of tumor cells that overexpress Notch. Overexpression
of the Notch signaling pathway plays an important role in tumor cell proliferation
and survival. The integral membrane protein GS is a multi-subunit protease complex
that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues
within their transmembrane domains and leads to their activation.;
UNII : LSK1L593UU;
CAS number : 1584647-27-7;
Molecule name : BMS-986115; AL 102; AL-102; WHG 626; WHG-626;
Semantic type(s)