Hedgehog (Hh)|Inhibitors Agonists Modulators Antagonists|HmoBio.com

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Hedgehog (Hh) is composed of N-terminal and C-terminal domains that dissociate in a self-catalyzed proteolytic cleavage reaction. The N-terminal product HhNp, modified by cholesterol during self-cleavage, harbors all known Hh signaling activities. When synthesized in the absence of the C-terminal domain (and hence lacking cholesterol modification), the N-terminal domain is aberrantly targeted and released selectively into the retina.

Hedgehog signaling pathway is linked to tumorigenesis and is aberrantly activated in a variety of cancers. Hh ligands bind to and suppress the transmembrane receptor Patched (PTCH), which suppresses Smoothened (SMO), a seven-transmembrane-helix protein that positively regulates the Hh pathway.

Sonic hedgehog (Shh) is a morphogen essential to the developing nervous system that continues to play an important role in adult life by contributing to cell proliferation and differentiation, maintaining blood-brain barrier integrity, and being cytoprotective against oxidative and excitotoxic stress, all features of importance in amyotrophic lateral sclerosis (ALS).

Indian hedgehog (Ihh), a signaling molecule that plays a pivotal role in the regulation of chondrocyte proliferation, maturation, and ossification both in long-bone development and digit joint formation, has also been found to be essential for temporomandibular joint (TMJ) development.

Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves.

Cat. No.	Product Name	CAS No.	Information
H8265	RU-SKI 43 hydrochloride	1782573-67-4	A small molecule inhibitor of Hhat (Hedgehog acyltransferase) with IC50 of 0.85 uM; specific to Shh palmitoylation and no effect for palmitoylation of H-Ras, Fyn and myristoylation of c-Src; reduces pancreatic cancer cell proliferation and Gli-1 activation through Smoothened-independent non-canonical signaling, inhibits two key proliferative pathways regulated by Akt and mTOR.
H8264	RU-SKI 43	1043797-53-0	A small molecule inhibitor of Hhat (Hedgehog acyltransferase) with IC50 of 0.85 uM; specific to Shh palmitoylation and no effect for palmitoylation of H-Ras, Fyn and myristoylation of c-Src; reduces pancreatic cancer cell proliferation and Gli-1 activation through Smoothened-independent non-canonical signaling, inhibits two key proliferative pathways regulated by Akt and mTOR.
H8263	Robotnikinin	1132653-79-2	Robotnikinin is asmall molecule that binds the extracellular Sonic Hedgehog (Shh) protein (Kd=3.1 uM) and blocks Shh-signaling in cell lines, human primary keratinocytes and synthetic model of human skin; displays significant repression of Shh-induced Gli1/Gli2, and interferes with the ability of the ShhN protein complex to relay its signal efficiently to Ptc1.
H8262	HPI-1	599150-20-6	HPI-1 is a Hedgehog (Hh) pathway inhibitor that suppresses signaling through Shh (IC50=1.5 uM) without significantly affecting Wnt signaling (IC50>30 uM); suppresses Hh activation induced by loss of Suppressor of Fused or by Gli overexpression; inhibits signaling through the oncogenic Smoothened (Smo) mutant SmoM2 in neuron precursors, preventing cell proliferation.
H8261	Cyclopamine tartrate	1178510-81-0	Cyclopamine tartrate is a natural steroidal alkaloid that inhibits hedgehog (Hh) signaling with IC50 of 46 nM; inhibits hedgehog-dependent expression of Pax7 with IC50 of 24 nM, blocks the response of neural plate explants to recombinant Shh-N; A useful tool in studying the role of Hh in normal development, and as a potential treatment for certain cancers in which Hh is overexpressed.
H8260	Cyclopamine	4449-51-8	A natural steroidal alkaloid that inhibits hedgehog (Hh) signaling with IC50 of 46 nM; inhibits hedgehog-dependent expression of Pax7 with IC50 of 24 nM, blocks the response of neural plate explants to recombinant Shh-N; A useful tool in studying the role of Hh in normal development, and as a potential treatment for certain cancers in which Hh is overexpressed.
H8259	Ciliobrevin A	302803-72-1	A small molecule Hedgehog pathway inhibitor (IC50=7 uM) that acts downstream of Su(fu) to modulate Gli processing, activation or trafficking; does not directly target Smo, blocks the proliferation of cerebellar granule neuron precursors expressing an oncogenic form of Smo; disrupts spindle pole assembly and kinetochore-microtubule attachment, inhibits melanosome aggregation and peroxisome motility in cultured cells; inhibits AAA+ ATPase motor cytoplasmic dynein.
H8258	BRD9526	1446352-30-2	BRD9526 is a potent, small-molecule inhibitor of the Sonic Hedgehog (Shh) pathway with EC50 of 60 nM, partially lowers Gli1 expression at concentrations of 10 uM, a useful probe of Shh signaling pathway.
H8257	BRD50837	1314295-24-3	BRD50837 is a potent, selective, small-molecule inhibitor of the Sonic Hedgehog (Shh) pathway with EC50 of 90 nM, partially lowers Gli1 expression at concentrations of 2 uM, a useful probe of Shh signaling pathway.
H8256	AY-9944	366-93-8	AY-9944 is a cholesterol biosynthesis inhibitor that targets the 7-dehydro cholesterol Δ7-reductase (DHCR7) enzyme (IC50=13 nM), attenuates of Smoothened-dependent and -independent Hh signaling; has been used to recapitulate phenotypes of Smith-Lemli-Opitz syndrome in animal model.

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