Gamma-secretase Inhibitor

Gamma-secretase inhibitor DBZ, originally synthesised by Syncom is nowadays a widely used tool compound for investigating of Notch signalling [Johan H. van Es, et al Nature 2005, 435, 959-963].

Notch genes encode large, single-transmembrane receptors that regulate a broad range of cell-fate decisions. Recently, the transmembrane receptor Notch has been shown to be expressed on the podocyte surface in the setting of animal and human glomerulopathies. Moreover, the Notch pathway is involved in the development of glomerular disease.
[Nature Reviews Drug discovery 2008, 7, 937]

 

DBZ is available from stock in gram quantities. For price information please send a request HERE

 

Gamma-secretase inhibitor DBZSIC-020042
Cas # [209984-56-5] DBZ
Purity > 99%
Chemical Formula: C26H23F2N3O3
Molecular Weight: 463.48

 

Chemical name: (S)-2-(2-(3,5-difluorophenyl)acetamido)-N-((S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)propanamide
Synonyms: DBZ, dibenzazepine, Gamma-secretase inhibitor, g-secretase inhibitor XX, GSI-XX, YO-01027 Deshydroxy LY-411575,

Note: This product is for R&D use only, not for drug, household, or other uses.

 

Syncom has a collection of advanced pharmaceutical intermediates, reference standards and the corresponding deuterated derivatives and regularly invests in the synthesis of new compounds to expand our product collection!.

If you are interested in a pharmaceutical reference standard that is not available from stock, Syncom can probably provide the compounds by custom synthesis.

 

FOR PRODUCT CITATIONS OF GAMMA-SECRETASE INHIBITOR DBZ SEE:

Use of gamma secretase inhibitors and notch pathway inhibitors for treatment and prevention of renal disease
Susztak, et al. US 2008/010362

Method for modulation the immune response by activating or inactivating the notch and/or stat4 signal path
Scheffold, Alexander et al US 8709710

Notch regulates IL-10 production by T helper 1 cells
Sascha Rutz et al PNAS 2008, 105, 3497–3502

Synergistic interaction of notch-1 inhibitors with glucocorticoids
Adolfo a Ferrando and Pedro J Real WO 2008112249 A1

Notch Signaling Is Required for Exocrine Regeneration After Acute Pancreatitis
Jens T. Siveke et al GASTROENTEROLOGY 2008,134, 544–555

g-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia
Pedro J Real, et al Nature Medicine 2009, 15, 50

Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans
Bernhard Bielesz et al The Journal of Clinical Investigation 2010, 120, 4040.

Treatment of an intestinal adenoma and/or adenocarcinoma by inhibition of notch pathway activation
Johannes Carolus Clevers et al US 2010/0292165 A1

Cutting Edge: Plasmacytoid Dendritic Cells Induce IL-10 Production in T Cells via the Delta-Like-4/Notch Axis
Nadine Kassner, et al The Journal of Immunology, 2010, 184, 550–554

Genetic Evidence That Intestinal Notch Functions Vary Regionally and Operate through a Common Mechanism of Math1 Repression
Tae-Hee Kim and Ramesh A. Shivdasani The Journal of Biological Chemistry  2011, 286, 11427–11433,

Hypoxia and lineage specification of cell line-derived colorectal cancer stem cells
Trevor M. Yeung et al PNAS 2011,  108, 4382

Notch signalling in stomach epithelial stem cell homeostasis
Tae-Hea Kim and Ramesh A Shivdasani J. Exp. Med. 2011 Vol. 208 No. 4 677-688

Cleavage of Notch1 by granzyme B disables its transcriptional activity
Geert van Tetering et al Biochem. J. 2011, 437, 313–322

Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells
Kelli L. VanDussen Development.  2012; 139m 488–497. doi:  10.1242/dev.070763

A Core Human Primary Tumor Angiogenesis Signature Identifies the Endothelial Orphan Receptor ELTD1 as a Key Regulator of Angiogenesis
Massimo Masiero et al Cancer cell 2013 24 229–241

Notch signaling regulates tubular morphogenesis during repair from biliary damage in mice
Romina Fiorotto et al  Journal of Hepatology 2013, 59, 124–130

Inhibition of Notch uncouples Akt activation from hepatic lipid accumulation by decreasing mTorc1 stability
Utpal B Pajvani et al Nature Medicine 2013, 19, 1054–106

Differential Roles of Hath1, MUC2 and P27Kip1 in Relation with Gamma-Secretase Inhibition in Human Colonic Carcinomas: A Translational Study
Frédérique Souazé et al PLOS ONE  2013, 8  Issue 2,  e55904

Aberrant Notch1-dependent effects on glomerular parietal epithelial cells promotes collapsing focal segmental glomerulosclerosis with progressive podocyte loss
Toshiharu Ueno et al Kidney International 2013, 83, 1065–1075; doi:10.1038/ki.2013.48

TRAF6 Stimulates the Tumor-Promoting Effects of TGFβ Type I Receptor Through Polyubiquitination and Activation of Presenilin 1
Shyam Kumar Gudey, et al Sci. Signal. 2014 7 (307), ra2. [DOI: 10.1126/scisignal.2004207]

Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity
Tea-Hee Kim at al Nature 2014, 506, 511–515

Leukaemogenesis induced by an activating b-catenin mutation in osteoblasts
Aruna Kode et al Nature 2014, 506, 240–244

A multiparametric approach to monitor the effects of g-secretase inhibition along the whole intestinal tract
Laure Droy-Dupré et al Disease Models & Mechanisms 2012, 5, 107-114 doi:10.1242/dmm.007591