HES4 Inhibitors
Chemical inhibitors of HES4 function by targeting the Notch signaling pathway, which is integral to the regulation of HES4 activity. γ-Secretase inhibitors such as DAPT, LY411575, RO4929097, PF-03084014, MK-0752, DBZ, Compound E, BMS-708163, L-685458, Semagacestat, MRK-560, and Begacestat impede the cleavage of Notch receptors. This cleavage is a prerequisite for the generation of the Notch intracellular domain (NICD), which translocates to the nucleus and contributes to the transcriptional activation of target genes, including HES4. By preventing the formation of NICD, these chemical inhibitors attenuate the Notch pathway signaling, thereby reducing the expression and functional activity of HES4.
The mechanism of action for these inhibitors involves the binding to the γ-secretase complex, rendering it unable to process the Notch receptor proteins. For instance, DAPT and LY411575 are known to bind to the active site of γ-secretase, leading to a decrease in the release of NICD. Similarly, RO4929097 and PF-03084014 selectively inhibit the γ-secretase-mediated cleavage, and thereby, the Notch signaling. The inhibition of this signaling pathway is crucial because it directly affects the transcriptional regulation activities where HES4 plays a role. With the Notch pathway subdued, the transcription and subsequent activity of HES4 are expected to decrease, leading to functional inhibition. The use of these chemical inhibitors effectively reduces the activity of γ-secretase, which in turn, is anticipated to lower the functional influence of HES4 in cellular processes that it normally regulates.
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
DAPT | 208255-80-5 | sc-201315 sc-201315A sc-201315B sc-201315C | 5 mg 25 mg 100 mg 1 g | $40.00 $120.00 $480.00 $2141.00 | 47 | |
DAPT is a γ-secretase inhibitor that prevents the cleavage of Notch proteins, a step required for their activation. By inhibiting γ-secretase, DAPT can reduce Notch signaling activity, which could decrease the functional activity of HES4 as it is a downstream target of Notch. | ||||||
LY411575 | 209984-57-6 | sc-364529 sc-364529A | 10 mg 50 mg | $198.00 $473.00 | 6 | |
LY411575 is another potent γ-secretase inhibitor. By inhibiting the γ-secretase complex, it prevents the production of active Notch intracellular domain (NICD), thereby reducing Notch pathway activity and subsequent HES4 function. | ||||||
RO-4929097 | 847925-91-1 | sc-364602 sc-364602A | 10 mg 50 mg | $439.00 $1417.00 | 1 | |
RO4929097 is a γ-secretase inhibitor that impedes the activation of Notch receptors. With reduced Notch activity, the transcriptional activation of HES4 is likely to be diminished, leading to functional inhibition. | ||||||
PF-3084014 | 1290543-63-3 | sc-507501 | 5 mg | $130.00 | ||
PF-03084014, known as Nirogacestat, is a selective γ-secretase inhibitor. It disrupts Notch receptor processing and can attenuate the expression of Notch pathway genes including HES4. | ||||||
MK-0752 | 471905-41-6 | sc-364534 sc-364534A | 10 mg 50 mg | $592.00 $1550.00 | ||
MK-0752 is a γ-secretase inhibitor that can decrease Notch signaling, which is essential for the regulation of HES4. By inhibiting Notch pathway activation, MK-0752 can indirectly inhibit HES4 activity. | ||||||
Dibenzazepine (Deshydroxy LY 411575) | 209984-56-5 | sc-207554 sc-207554A | 2 mg 5 mg | $235.00 $260.00 | 4 | |
DBZ, or dibenzazepine, is a γ-secretase inhibitor that can arrest Notch receptor cleavage and activation, leading to a potential functional decrease in HES4 activity due to reduced Notch pathway signaling. | ||||||
Compound E | 209986-17-4 | sc-221433 sc-221433A sc-221433B | 250 µg 1 mg 5 mg | $124.00 $342.00 $967.00 | 12 | |
Compound E is a potent, selective γ-secretase inhibitor, which can prevent the cleavage of the Notch receptor, thereby possibly reducing the functionality of HES4. | ||||||
BMS-708163 | 1146699-66-2 | sc-364444 sc-364444A | 10 mg 50 mg | $480.00 $1455.00 | 1 | |
BMS-708163, known as Avagacestat, is a γ-secretase inhibitor that reduces Notch signaling and could thereby functionally inhibit HES4, which is regulated by Notch signaling. | ||||||
L-685,458 | 292632-98-5 | sc-204042 sc-204042A | 1 mg 5 mg | $337.00 $1000.00 | 4 | |
L-685458 is an inhibitor of γ-secretase, which can reduce the production of active Notch, potentially leading to decreased activity of HES4 as part of the Notch signaling cascade. | ||||||
Semagacestat | 425386-60-3 | sc-364614 sc-364614A | 10 mg 50 mg | $350.00 $1200.00 | 1 | |
Semagacestat is a γ-secretase inhibitor that blocks Notch signaling. By impeding the activation of Notch, it could functionally inhibit the activity of HES4. | ||||||