DBZ, 10 mg

A diazepine-based γ-secretase inhibitor supplied by STEMCELL Technologies, this small molecule blocks γ-secretase–mediated cleavage of transmembrane proteins including Notch, amyloid precursor protein (APP), and Ephrin-B2. By inhibiting γ-secretase, the compound prevents formation of the Notch intracellular domain, the active signalling effector of Notch, with an IC₅₀ of 1.7 nM (Milano et al.). It is also known as Dibenzazepine or YO-01027 (CAS 209984-56-5), with molecular formula C₂₆H₂₃F₂N₃O₃ and a molecular weight of 463.5 g/mol. The product is provided as a crystalline solid with a purity of ≥ 98% and is used as part of workflows for mouse intestinal organoid culture.

The inhibitor has been applied across diverse research areas. In reprogramming, it enables generation of induced pluripotent stem cells from human keratinocytes in the absence of the oncogenic factors KLF4 and c-MYC (Ichida et al.). In differentiation studies, it induces intestinal cell apoptosis and goblet cell metaplasia in rats and attenuates the reduction of paneth and goblet cells caused by TSC2 inhibition. In cancer models, the compound promotes differentiation of intestinal adenomas in Apc(Min) transgenic mice and reduces graft-versus-host disease severity after bone marrow transplantation in mice by lowering inflammatory cytokine production. Metabolic studies report improved glucose homeostasis and a shift toward fat utilization in mice. In disease modeling, the inhibitor reduces Aβ40 levels by 71% in an APP transgenic mouse model, lessens brain injury in a mouse ischemia-reperfusion stroke model, and attenuates renal fibrosis in a unilateral ureteral obstruction model.

The compound is soluble in DMSO at concentrations up to 95 mM and has low aqueous solubility. For cell culture use, stock solutions should be diluted into medium immediately before use, with final DMSO kept below 0.1% to avoid cell toxicity. Stock solutions should be prepared fresh, stored at -20°C, and aliquoted to limit freeze-thaw cycles. The product is stable at -20°C as supplied and should be protected from prolonged light exposure.