The mammalian Notch signaling pathway consists of three main components: Notch receptors, ligands that bind to Notch receptors, and downstream effectors of Notch signaling. In mammals, four Notch receptors exist, including Notch1, Notch2, Notch3, and Notch4. Notch receptor is a transmembrane protein mainly consisting of Notch extracellular domain (NECD), transmembrane domain (TMD), and intracellular domain (NICD).
Ligand-activated Notch receptors initiate transcription of downstream target genes by interacting with DNA-bound CBF-1/suppressor of hairless/Lag1 (CSL)-corepressor complexes, forming the canonical Notch signaling pathway. Alternatively, Notch may act through a non-canonical pathway independent of ligands or CSL. The canonical Notch signaling pathway plays a major physiological role in intercellular interaction and gene transcriptional regulation, while non-classical Notch signaling involves the crosstalk between various signaling pathways to execute the activation of target genes.
Amerigo Scientific offers a variety of high-purity Notch signaling inhibitors, including EZH2 inhibitor and γ-secretase inhibitors to advance Notch signaling pathway investigations in disease etiology and novel therapeutic development.
Notch Signaling Inhibitors
Notch signaling is essential for embryonic development and tissue homeostasis. Dysregulation of Notch signaling contributes to human diseases, including a variety of developmental disorders, neurological disorders, and cancers.
| Product |
Description |
CAS Number |
|
IMR-1
|
Notch signaling inhibitor |
310456-65-6 |
|
FLI-06
|
Notch signaling inhibitor |
313967-18-9 |
| LY3039478
|
Notch inhibitor (potent) |
1421438-81-4 |
Enhancer of Zeste Homolog 2 (EZH2) Inhibitors
Polycomb repressive complex 1 (PRC1) and Polycomb repressive complex 2 (PRC2) are two major core protein complexes in mammalian cells. As a catalytic subunit of PRC2, enhancer of zeste homolog 2 (EZH2) represses gene expression by methylating lysine 27 of histone 3 (H3K27). EZH2 has the ability to directly methylate a variety of target molecules, including GATA4, STAT3, β-catenin and Lysins at positions 510, 514 and 515 of PRC2. EZH2 can also directly bind to specific molecules, forming a ternary complex with Rel a and Rel B within the NF-κB component, interacting with TCF, β-catenin and ER, and activating c-Myc and cyclin D1 genes located downstream. In addition, EZH2 binds to the promoter region of target genes, affecting gene transcription. Studies have shown that EZH2 plays a key role in the regulation of Notch, JNK/STAT3, and Wnt/β-catenin signaling pathways.
γ-secretase Inhibitors
γ-secretase belongs to the family of intramembrane cleavage proteases (i-CLiPs) that carry out hydrolysis of substrates within the hydrophobic environment of the lipid bilayer. γ-secretase is mainly involved in the intramembranous proteolysis of type I membrane proteins. It can cleave many important functional proteins, such as APP, Notch, E-cadherin, ErbB4, CD44, tyrosinase, TREM2, and Alcadein.
γ-secretase is an important component of Notch signaling pathway. During Notch cleavage, γ-secretase releases a Notch intracellular domain (NICD) in the cytosol. NICD can translocate into the nucleus and regulate gene transcription. Therefore, one mothed to effectively block Notch activity is to prevent its cleavage at the cell surface with γ-secretase inhibitors.
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