NUMB Inhibitors
The compounds identified as NUMB inhibitors encompass a class of gamma-secretase inhibitors, each structurally tailored to intervene in the proteolytic processing of the Notch receptor. By inhibiting gamma-secretase, these molecules maintain high levels of the Notch precursor, thereby hindering the formation of the Notch intracellular domain (NICD), which is crucial for translocating to the nucleus and initiating transcription of downstream targets. Since NUMB acts as a natural antagonist to Notch by promoting the maturation of neuronal progenitor cells and restricting developmental, the presence of these inhibitors indirectly impairs NUMB's function. In essence, the elevation of NICD resulting from gamma-secretase inhibition causes a feedback mechanism that diminishes the ability of NUMB to counterbalance Notch signaling, thereby leading to an inadvertent reduction in NUMB-mediated cell fate determination during embryogenesis.
The biochemical footprint of these inhibitors lies in their shared ability to modulate Notch receptor cleavage. This key interaction within the Notch signaling pathway orchestrates a cascade of cellular events that directly affect NUMB's role in cell fate specification. By meticulously blocking the cleavage step facilitated by gamma-secretase, the inhibitors collectively ensure that NICD levels remain unproductively high, thereby stymieing the transcriptional events that would otherwise be initiated by NICD's nuclear activity. The altered biochemical landscape resulting from the inhibition of Notch signaling creates a milieu wherein NUMB is unable to effectively perform its antagonistic function, thereby providing an indirect modulatory influence over NUMB's role in the neurogenic processes. This chemical class exhibits a precision-targeted approach to modulating Notch signaling, demonstrating a distinct biochemical interaction that leads to the downregulation of NUMB functionality, with broad implications for cellular development and maturation in the context of embryonic neurogenesis.
| 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 | $99.00 $335.00 $836.00 $2099.00 | 47 | |
Gamma-secretase inhibitor DAPT prevents the cleavage of many proteins, including Notch. By inhibiting Notch, it indirectly affects NUMB by disrupting the Notch-NUMB negative feedback loop, leading to an accumulation of Notch intracellular domain (NICD) levels and a subsequent decrease in NUMB function, which is required for differentiation over proliferation in cellular development. | ||||||
L-685,458 | 292632-98-5 | sc-204042 sc-204042A | 1 mg 5 mg | $337.00 $1000.00 | 4 | |
This compound is a gamma-secretase inhibitor that prevents the proteolytic release of NICD from the Notch receptor. By doing so, it indirectly inhibits NUMB activity as NUMB is a known antagonist of Notch signaling. Inhibition of Notch signaling leads to an increase in NICD levels and a reduction in NUMB’s ability to restrict developmental potential and promote INP cell maturation. | ||||||
RO-4929097 | 847925-91-1 | sc-364602 sc-364602A | 10 mg 50 mg | $430.00 $1389.00 | 1 | |
RO4929097 inhibits gamma-secretase, impacting Notch receptor cleavage and modulating its signaling pathway. The inhibition of Notch signaling by this compound reduces the negative influence on NUMB, thereby lowering NUMB’s function which is to antagonize Notch signaling for the promotion of neural differentiation. | ||||||
Dibenzazepine (Deshydroxy LY 411575) | 209984-56-5 | sc-207554 sc-207554A | 2 mg 5 mg | $100.00 $260.00 | 4 | |
As a potent gamma-secretase inhibitor, LY411575 blocks the production of NICD by preventing the cleavage of the Notch receptor. The inhibition of Notch signaling allows for the decreased activity of NUMB, as NUMB’s role is to regulate cell fate by acting as an antagonist to Notch signaling. | ||||||
MK-0752 | 471905-41-6 | sc-364534 sc-364534A | 10 mg 50 mg | $592.00 $1550.00 | ||
MK-0752 serves as a gamma-secretase inhibitor, disrupting Notch signaling. By inhibiting the cleavage and activation of the Notch receptor, it lowers the antagonistic activity of NUMB on Notch signaling, which is crucial for the balance between cell differentiation and proliferation in neuronal progenitors. | ||||||
PF-3084014 | 1290543-63-3 | sc-507501 | 5 mg | $130.00 | ||
PF-03084014, a gamma-secretase inhibitor, affects Notch receptor processing and alters its signaling. It indirectly modulates NUMB by influencing Notch signaling, which NUMB antagonizes, thus affecting NUMB’s role in the differentiation and maturation of INP cells. | ||||||
Compound E | 209986-17-4 | sc-221433 sc-221433A sc-221433B | 250 µg 1 mg 5 mg | $122.00 $335.00 $948.00 | 12 | |
Compound E inhibits gamma-secretase, thus affecting the Notch signaling cascade. By hindering the Notch pathway, it indirectly modulates NUMB’s activity, since NUMB functions as an antagonist of Notch to control cell fate decisions in neurogenesis. | ||||||
BMS-708163 | 1146699-66-2 | sc-364444 sc-364444A | 10 mg 50 mg | $480.00 $1455.00 | 1 | |
BMS-708163 is a gamma-secretase inhibitor that indirectly reduces NUMB function by preventing the proteolytic release of NICD, which is essential for the activation of Notch signaling. NUMB, being a Notch antagonist, is affected due to the perturbation of this pathway. | ||||||
Semagacestat | 425386-60-3 | sc-364614 sc-364614A | 10 mg 50 mg | $350.00 $1200.00 | 1 | |
By inhibiting gamma-secretase, Semagacestat disrupts Notch receptor processing. This results in altered Notch signaling, which indirectly diminishes the activity of NUMB. NUMB’s primary role is to antagonize Notch signaling in the regulation of neuronal cell fate and maturation. | ||||||