117) have shown that a cocktail of secretase
inhibitors affects A[beta] levels in an additive manner.
Our drug candidates selectively modulate gamma secretase
, the enzyme generating the neurotoxic peptides that form amyloid beta plaques, the signature of this debilitating disease.
Due to the complexity of the Notch signalling that leads up to the cleavage by gamma secretase
, it is proposed that Notch inhibition can be achieved on multiple levels.
Bristol-Myers, based in New York, also has an earlier-stage gamma secretase
His findings show that, when damaged or excessively activated in human cells, Ras, through gamma secretase
, activates a protein known as Notch-1, which in turn triggers a chain of events that allow cancer cells to grow.
EnVivo Pharmaceuticals, a company dedicated to developing a broad range of novel central nervous system (CNS) therapies, today announced the initiation of a Phase 2 clinical trial of EVP-0962, its potent and selective gamma secretase
modulator (GSM), in healthy volunteers and in volunteers with mild cognitive impairment or early Alzheimer's disease.
Osipo, "Gamma secretase
inhibitors of Notch signaling," OncoTargets and Therapy, vol.
The two next-generation classes of compound that are currently in clinical trials target an enzyme that cuts APP, known as gamma secretase
Pratico said that their research has shown that 12/15-Lipoxygenase controls Beta secretase
(BACE-1), an enzyme that is key to the development of amyloid plaques in Alzheimer's patients.
Over the past few years, most of the new drugs focus on an enzyme, gamma secretase
that snips a big protein to produce beta amyloid.
Furthermore, they demonstrated that Notch signalling directly stimulated survivin gene expression, and also that inhibition of the enzyme gamma secretase
(a key enzyme in the Notch signalling pathway) with GSI in ER-negative breast cancer cells abolished colony formation in soft agar and induced apoptosis.
The licensing agreement for BAN2401, together with the gamma secretase
modulator E2012 developed in-house by Eisai, allows the Company to pursue parallel approaches to developing next-generation treatments for Alzheimer's disease based on a small molecule compound and immunotherapy.