Hedgehog Signaling

The Hedgehog (Hh) signaling pathway is a fundamental regulator of embryonic development across animal species. Initial discoveries of Hh signaling came from studies in Drosophila, where it was shown to be critical for both embryogenesis and metamorphosis.

In mammals, the pathway is mediated by three homologous proteins: Sonic Hedgehog (SHH), Desert Hedgehog (DHH), and Indian Hedgehog (IHH). Among these, SHH is the most extensively characterized. SHH interacts with its receptor, Patched-1 (PTCH1), a transmembrane protein. In the absence of SHH, Patched-1 suppresses the activity of Smoothened (SMO), a nearby signaling molecule. Binding of SHH to Patched-1 relieves this inhibition, allowing Smoothened to activate downstream GLI transcription factors—Gli1 and Gli2 functioning as transcriptional activators, and Gli3 as a repressor. Activated GLI proteins translocate into the nucleus, where they regulate the expression of genes essential for processes such as embryogenesis, limb formation, adult stem cell maintenance, and hair follicle cycling.

Disruptions in Hh signaling are associated with a wide spectrum of diseases. Suppression of pathway activity during fetal development can lead to holoprosencephaly, a severe developmental disorder that in extreme cases results in cyclopia. Conversely, aberrant activation of Hh signaling has been linked to tumorigenesis, likely by driving the conversion of adult stem cells into malignant cancer stem cells. Beyond cancer initiation, Hh signaling may also contribute to angiogenesis and tumor metastasis. As a result, targeted inhibitors of pathway components are being developed as potential anticancer therapies.

Hedgehog signaling inhibitors:

· C120126 C409109– Calcitriol: ≥97%; 10mM in DMSO

· C140600 C463317 C400222 C110685 C477437 C395975 C400271 C408195  Curcumin: ≥65% , ≥95%,≥75%(Curcumin) total curcumin content, Natural extraction (isomer mixture), Analytical standard, Curcumin from Curcuma longa (Turmeric),powder, 0.1% in 95% Ethanol, Curcumin from Synthetic ≥98% , 10mM in DMSO

· F127328 C409070 – Forskolin: ≥98%; 10mM in DMSO

· G106673 G106672 G408928 – Genistein: ≥97%, analytical standard ≥98%, 10mM in DMSO

· I129798 I427215  – Imiquimod: ≥98%; 2mM in DMSO

· R106320 R106321 T409019–Retinoic acid: ≥98%, analytical standard, 10mM in DMSO

· V274917 V425030 – Veratramine: ≥98%; 10mM in DMSO

Smoothened modulators:

· B139120 B408884 – Berberine Hydrochloride Hydrate: ≥95%; 10mM in DMSO

· C125994 – Cyclopamine: ≥99%

· V127477 V408303 – GDC-0449: ≥98%; 10mM in DMSO

· I129771 I426206 – Itraconazole: ≥98%; 2mM in DMSO

· J664401 J135916 J424100 – Jervine: ≥98%, ≥97%, 10mM in DMSO

· S649283 S655786 – Sonidegib diphosphate: ≥99%; 10mM in DMSO

· P126030 P424198 – Purmorphamine: ≥98%; 2mM in DMSO

References:

1. Singh BN, Koyano-Nakagawa N, Donaldson A, et al. Genes (Basel). 2015 Jun 23;6(2):417-35.

2. Lee ST, Welch KD, Panter KE, et al. J Agric Food Chem. 2014 Jul 30;62(30):7355-62.

3. Shimizu T, Nakagawa K. Nihon Rinsho. 2015 Aug;73(8):1342-8.

4. Velcheti V. Med Hypotheses. 2007;69(4):948-9.

Aladdin: https://www.aladdinsci.com/