YO-01027 (Dibenzazepine) (GMP) is YO-01027 synthesized following Good Manufacturing Practice (GMP) standards. GMP-compliant small molecules serve effectively as ancillary agents in the production of cell therapies. YO-01027 acts as a potent inhibitor of γ-secretase [1][2].
体内研究
DBZ inhibits activated Notch1 signaling in abdominal aortic aneurysm (AAA) tissue from both Ang II-infused Apo E-/- mice and humans undergoing AAA repair. DBZ significantly reduces Ang II-stimulated accumulation of macrophages and CD4+ T cells, inhibits ERK-mediated angiogenesis, and concurrently reverses Th2 response, in vivo[3].
Administration of DBZ significantly reduces renal fibrosis and the expression of fibrotic markers, such as collagen 1α1/3α1, fibronectin, and α-smooth muscle actin (α-SMA). DBZ effectively suppresses the expression of transforming growth factor (TGF)-β, phosphorylated Smad 2, and Smad 3 induced by ureteral obstruction [4].
体外研究
Elevating levels of DBZ administered to cells expressing APPL or Notch result in a gradual buildup of APPL CTF fragments and a reduction in NICD production, following a strictly dose-dependent pattern[1].
CE and DBZ target the N-terminal fragment of presenilin 1 within the γ-secretase complex[2].
YO-01027 (0.25-10 μM, during 1-18 days) enhances the generation of induced pluripotent stem cells (iPSCs) from human neonatal keratinocytes [2].
YO-01027 (at 2 μM for 3 days) does not alter p53 activity in human keratinocytes transduced with OCT4 and SOX2 [2].
YO-01027 (10 μM, 3 days) enhances the proliferation of supporting cells (SCs) in cultured mouse cochleae [3].
YO-01027 (10 μM, 3 days) induces the generation of new hair cells (HCs) and augments the total number of HCs in neonatal mouse cochleae [3].
YO-01027 细胞实验
Cell Line
Concentration
Treated Time
Description
References
YUMM1.7 mouse melanoma cells
25 µg/ml
3 days
Anti-Notch1 induced 80% cell death
J Exp Clin Cancer Res. 2024 Nov 4;43(1):295.
YUMM2.1 mouse melanoma cells
25 µg/ml
3 days
Anti-Notch1 induced 55% cell death
J Exp Clin Cancer Res. 2024 Nov 4;43(1):295.
K457 human melanoma cells
25 µg/ml
3 days
Anti-Notch1 induced 75% cell death
J Exp Clin Cancer Res. 2024 Nov 4;43(1):295.
Enteroids
5 mM
10 days
To examine the impact of YO-01027 on enteroid formation and self-renewal.
Stem Cell Reports. 2022 May 10;17(5):1138-1153.
B16F10 melanoma cells
25 μg/ml and 50 μg/ml
24 hours
The cytotoxic effect of combined therapies was evaluated, showing significant reduction in cell viability and increased apoptosis.
Nanoscale Res Lett. 2020 May 19;15(1):113.
Colon normal organoids
2.5 µM
48 hours
To investigate the effect of Notch signaling blockade on the differentiation of colon normal organoids, results showed that DBZ promoted the differentiation of secretory goblet cells.
Cell Death Dis. 2024 Apr 29;15(4):301.
Colon tumor organoids
5 µM
72 hours
To investigate the effect of Notch signaling blockade on the differentiation of colon tumor organoids, results showed that DBZ failed to induce any mucosecretory gene expression.
Cell Death Dis. 2024 Apr 29;15(4):301.
YO-01027 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
YUMM2.1 and YUMM1.7 mouse melanoma models
Intraperitoneal injection
10 mg/kg
Every other day for 15 days
Anti-Notch1 significantly delayed tumor growth and altered the TME, reducing immunosuppressive cells and increasing CD8+ T cells
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