Gamma Secretase Inhibitors and Modulators

Agents that suppress GAMMA-SECRETASE by inhibiting or modulating its activities. Targeted enzymatic activities include its involvement in accumulation of toxic AMYLOID BETA-PEPTIDES (e.g., Aβ42) in ALZHEIMER DISEASE and activation of NOTCH RECEPTOR mediated SIGNAL PATHWAYS in certain cancer types.

Also Known As:

Secretase Inhibitors, Gamma; Secretase Modulators, Gamma; GS Inhibitors; GS Inhibitors and Modulators; GS Modulators; Gamma Secretase Inhibitors; Gamma Secretase Modulators

Networked: 156 relevant articles (4 outcomes, 10 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Chemical Actions and Uses
- Pharmacologic Actions: 160
  - Molecular Mechanisms of Pharmacological Action: 24
    - Enzyme Inhibitors: 1659
      - Gamma Secretase Inhibitors and Modulators: 156

Experts

1.	Zhang, Lili: 7 articles (01/2013 - 12/2006)
2.	Harrison, Timothy: 7 articles (02/2007 - 01/2003)
3.	Song, Lixin: 6 articles (01/2013 - 01/2007)
4.	Clader, John W: 6 articles (01/2008 - 12/2006)
5.	Lewis, Huw D: 6 articles (02/2007 - 01/2003)
6.	Tohda, Shuji: 5 articles (10/2010 - 11/2006)
7.	Shearman, Mark S: 5 articles (04/2010 - 06/2003)
8.	Look, A Thomas: 5 articles (03/2010 - 02/2007)
9.	Pissarnitski, Dmitri A: 5 articles (01/2008 - 01/2007)
10.	Zhao, Zhiqiang: 5 articles (01/2008 - 01/2007)

Related Diseases

1.	Alzheimer Disease (Alzheimer's Disease) 02/01/2005 - "gamma-Secretase inhibitors are one promising approach to the development of a therapeutic for Alzheimer's disease (AD). " 03/22/2010 - "Several gamma-secretase inhibitors (GSI) are in clinical trials for the treatment of Alzheimer's disease (AD). " 01/01/2023 - "Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease." 08/17/2022 - "Our observations shed light on the important mechanics of the fascinating GS architecture and may contribute to propose new GS modulators able to impact on the Alzheimer's disease treatment." 10/01/2019 - "Gamma secretase modulators and BACE inhibitors reduce Aβ production without altering gene expression in Alzheimer's disease iPSC-derived neurons and mice."
2.	Neoplasms (Cancer) 01/01/2021 - "Gamma Secretase Inhibitors in Cancer: A Current Perspective on Clinical Performance." 11/01/2014 - "Using patient-derived xenograft models, we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. " 01/01/2014 - "Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents) could potentially affect myocardial repair. " 01/01/2010 - "NOTCH blockade by gamma-secretase inhibitors (GSIs) reduced neurosphere growth and clonogenicity in vitro, whereas expression of an active form of NOTCH2 increased tumor growth. " 12/29/2009 - "Finally, primary epithelial cell cultures, derived from NSCLC harboring constitutive activation of the Notch pathway, are selectively killed by inhibitors of Notch (gamma-secretase inhibitors), showing that the proliferative advantage of these tumors is dependent upon Notch signaling. "
3.	Glioma (Gliomas) 01/01/2019 - "In this study, we evaluated the effect of NOTCH signaling intervention by gamma-secretase inhibitors (GSIs) on glioma sphere-forming cells (GSCs). " 01/01/2010 - "In this study, we show that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) renders the glioma stem cells more sensitive to radiation at clinically relevant doses. " 09/01/2010 - "Notch activity is upregulated in many gliomas and can be suppressed using gamma-secretase inhibitors (GSI). " 11/25/2008 - "This work highlights the importance of p75(NTR) as a therapeutic target, suggesting that gamma-secretase inhibitors may have direct clinical application for the treatment of malignant glioma." 11/25/2008 - "Expression of cleavage-resistant chimeras of p75(NTR) or treatment of animals bearing p75(NTR)-positive intracranial tumors with clinically applicable gamma-secretase inhibitors resulted in dramatically decreased glioma invasion and prolonged survival. "
4.	Breast Neoplasms (Breast Cancer) 01/05/2012 - "Gamma-secretase inhibitors target tumor-initiating cells in a mouse model of ERBB2 breast cancer." 07/01/2010 - "Notch pathway activation is also common in this breast cancer subtype and can be suppressed by gamma-secretase inhibitors, which effectively block receptor cleavage and activation. " 06/16/2009 - "We tested the effect of three different gamma-secretase inhibitors (GSIs) in breast cancer cells. " 03/15/2013 - "Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors." 01/01/2013 - "Since CSCs are highly resistant to chemotherapy, additional treatment of breast cancer patients with CSC-specific drugs, such as salinomycin and gamma-secretase inhibitors which target the Wnt or Notch pathway, respectively, will be required. "
5.	Cognitive Dysfunction 01/01/2022 - "Despite the focus on GS inhibition, multiple GS inhibitors (GSIs) have failed in clinical trials as a result of side effects including exacerbated cognitive decline. "

Related Drugs and Biologics

1.	O-(glucuronic acid 2- sulfate)- (1- - 4)- O- (2,5)- anhydromannitol 6-sulfate
2.	Amyloid (Amyloid Fibrils)
3.	piperidine
4.	Amyloid Precursor Protein Secretases (beta-Secretase)
5.	Proteins (Proteins, Gene)
6.	Enzymes
7.	Catenins
8.	Metalloproteases (Metalloproteinases)
9.	Neuregulin-1 (Neuregulin 1)
10.	Docetaxel (Taxotere)

Related Therapies and Procedures

1.	Therapeutics
2.	Drug Therapy (Chemotherapy)