Hedgehog Signaling

The Hedgehog (Hh) signaling pathway is crucial in the development of all animals. In the embryo, it regulates morphogenesis of a variety of tissues and organs; in the adult, it controls stem cell proliferation. There are three known human Hh proteins: Shh, Dhh and Ihh.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
1639 AY 9944 dihydrochloride
Inhibitor of Hedgehog (Hh) signaling. Inhibits Δ7-dehydrocholesterol reductase
4838 AZ 12080282 dihydrochloride
Inhibitor of Hedgehog (Hh) signaling
4529 Ciliobrevin A
Hedgehog (Hh) pathway antagonist, inhibits ciliogenesis; also inhibits dynein
1623 Cyclopamine
Inhibitor of Hedgehog (Hh) signaling
5695 Eggmanone
Suppresses hedgehog signaling downstream of smoothened; also PDE4 inhibitor
3889 GANT 58
GLI1 antagonist; inhibits Hedgehog (Hh) signaling
3191 GANT 61
GLI antagonist; inhibits Hedgehog (Hh) signaling
3839 HPI 1
Inhibits Hedgehog signaling
5554 IHR 1
Potent Smo antagonist
5561 IHR-Cy3
Potent fluorescent Smo antagonist
4717 Jervine
Inhibitor of Hedgehog (Hh) signaling; binds directly to Smo
3341 JK 184
Downstream Hedgehog (Hh) signaling pathway inhibitor; inhibits alcohol dehydrogenase 7
4917 M 25
Potent Smoothened (Smo) receptor antagonist
4585 MRT 10
Smoothened (Smo) antagonist
5262 PF 5274857 hydrochloride
High affinity and selective Smoothened (Smo) receptor antagonist
4886 RU-SKI 43 hydrochloride
Hedgehog acyltransferase (Hhat) inhibitor; cell permeable
1974 SANT-1
Inhibitor of hedgehog (Hh) signaling; antagonizes smoothened activity
3617 SANT-2
Inhibitor of Hedgehog (Hh) signaling; antagonizes smoothened activity
4662 SMANT hydrochloride
Inhibits Smoothened (Smo) accumulation
1638 U 18666A
Inhibitor of Hedgehog (Hh) signaling. Also inhibits cholesterol synthesis

Activators

Cat No Product Name / Activity
4474 20(S)-Hydroxycholesterol
Allosteric activator of Hedgehog (Hh) signaling; induces Smo accumulation
4366 SAG
Activates the Hedgehog signaling pathway; potent Smoothened receptor agonist
5282 SAG 21k
Hedgehog signaling activator; brain penetrant and orally bioavailable

Other

Cat No Product Name / Activity
3267 Thiostrepton
Downregulates FOXM1

The Hedgehog (Hh) signaling pathway is crucial in the development of all known animals. In the embryo, it regulates morphogenesis of a variety of tissues and organs; in the adult, it controls stem cell proliferation.

There are three human Hh proteins: Sonic hedgehog (Shh), Desert hedgehog (Dhh) and Indian hedgehog (Ihh). Each is expressed at different times of development and in specific cell types and they are tightly controlled by highly complex, yet divergent transcriptional enhancers. Hh protein release and diffusion is controlled by various proteins including Skinny hedgehog (Sit), Dispatched (Disp), Tout-velu (Ttv) and Hedgehog-interacting protein (Hip). Hh proteins bind to the twelve transmembrane domain protein, Patched (Ptc). In the absence of Hh proteins, Ptc catalytically inhibits Smo. Hh-Ptc binding results in loss of Ptc activity and activation of Smo, which transduces the Hh signal to the cytoplasm. This leads to the activation of the Ci/Gli family of transcription factors, through complex interactions of Costal2 (Cos2), Fused (Fu) and Suppressor of fu [Su(fu)]. Furthermore, PKA, CK1, GSK-3 and Slimb modulate this signal transduction pathway.

Aberrant activation of the Hh pathway has been linked to multiple types of human cancer, particularly basal cell carcinoma. Disruption of Hh signaling during embryonic development, either through congenital mutation or maternal teratogen consumption, can lead to severe developmental disorders such as holoprosencephaly.

Literature for Hedgehog Signaling

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Stem Cells

Stem Cells Scientific Review

Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.

Hedgehog Signaling Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Shh Human SHH NM_000193 Q15465
Mouse Shh NM_009170 Q62226
Rat Shh NM_017221 Q63673
Dhh Human DHH NM_021044 O43323
Mouse Dhh NM_007857 Q61488
Rat Dhh XM_343327 Q9WUP6
Ihh Human IHH NM_002181 Q14623
Mouse Ihh NM_010544 P97812
Rat Ihh NM_053384 Q9ESH3
Smo Human SMO NM_005631 Q99835
Mouse Smo NM_176996 P56726
Rat Smo NM_012807 P97698
Patched 1 Human PTCH1 NM_000264 Q13635
Mouse Ptch1 NM_008957 Q61115
Rat Ptch1 NM_053566 Q6UY90
Patched 2 Human PTCH2 NM_003738 Q9Y6C5
Mouse Ptch2 NM_008958 O35595
Rat Ptch2 NM_001108975 XP_345571
Dispatched 1 Human DISP1 NM_032890 Q96F81
Mouse Disp1 NM_026866 Q3TDN0
Dispatched 2 Human DISP2 NM_033510 A7MBM2
Mouse Disp2 NM_170593 Q8CIP5
Rat Disp2 NM_001107759 XP_230531
Tout-velu Human EXT1 NM_000127 Q16394
Mouse Ext1 NM_010162 P97464
Rat Ext1 XM_216920 Q3B8R0
Hip Human Hhip NM_022475 Q96QV1
Mouse Hhip NM_020259 Q7TN16
Rat Hhip XM_238042 XP_238042
Gli1 Human GLI1 NM_005269 P08151
Mouse Gli1 NM_010296 P47806
Rat Gli1 XM_345832 Q91WY6
Gli2 Human GLI2 NM_005270 P10070
Mouse Gli2 NM_001081125 NP_001074594
Rat Gli2 NM_001107169 XP_222557
Gli3 Human GLI3 NM_000168 P10071
Mouse Gli3 NM_008130 Q61602
Rat Gli3 XM_225411 Q91WY5
Su(fu) Human SUFU NM_016169 Q9UMX1
Mouse Sufu NM_015752 Q9Z0P7
Rat Sufu NM_001024899 Q4V8C6