SAG

Hedgehog pathway activator; Activates Smoothened (SMO)

SAG

Hedgehog pathway activator; Activates Smoothened (SMO)

From: 194 USD
Catalog #
73412_C
Hedgehog pathway activator; Activates Smoothened (SMO)

Overview

SAG (Smoothened Agonist) is a chlorobenzothiophene-containing compound which acts as an activator of the G protein-coupled receptor Smoothened (SMO, EC₅₀ = 3 nM; Chen et al.) SMO is a component of the Hedgehog signaling pathway, which is translocated to the primary cilium after stimulation of the Patched receptor by Hedgehog family ligands, leading to pathway activation. SAG activates SMO via direct binding to the heptahelical bundle (Kd = 59 nM), stabilizing a specific conformation of SMO in cilia and leading to increased downstream gene expression (Rohatgi et al.). SAG abrogates cyclopamine inhibition of SMO, indicating that it acts downstream of cyclopamine (Frank-Kamenetsky et al.; Chen et al.; Lewis & Krieg).

DIFFERENTIATION
· Improves neuronal differentiation of human induced pluripotent stem cells (Mak et al.).

MAINTENANCE
· Induces proliferation and survival of neuronal and glial precursors in vitro and in vivo (Bragina et al.).
· Prevents glucocorticoid neurotoxicity in Math1-Cre, SmoM2 transgenic mice (Heine et al.).
· Rescues cerebellar size and behavioral phenotypes in the Ts65Dn mouse model of Down Syndrome (Das et al.).
Alternative Names
Smoothened Agonist
Cell Type
Neural Cells, PSC-Derived, Neural Stem and Progenitor Cells, Pluripotent Stem Cells
Species
Human, Mouse, Rat, Non-Human Primate, Other
Application
Differentiation, Expansion, Maintenance
Area of Interest
Disease Modeling, Neuroscience, Stem Cell Biology
CAS Number
912545-86-9
Chemical Formula
C₂₈H₂₈ClN₃OS
Molecular Weight
490.1 g/mol
Purity
≥ 98%
Pathway
Hedgehog
Target
SMO

Protocols and Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Product Name
SAG
Catalog #
73412, 73414
Lot #
All
Language
English
Product Name
SAG
Catalog #
73414
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
SAG
Catalog #
73412, 73414
Lot #
All
Language
English

Applications

This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.

Resources and Publications

Educational Materials (2)

Publications (8)

Reagents for developmental regulation of Hedgehog signaling. Lewis C and Krieg PA Methods (San Diego, Calif.) 2014 APR

Abstract

We have examined a number of reagents for their ability to modulate activity of the Hh signaling pathway during embryonic development of Xenopus. In particular we have focused on regulation of events occurring during tailbud stages and later. Two inducible protein reagents based on the Gli1 and Gli3 transcription factors were generated and the activity of these proteins was compared to the Hh signaling pathway inhibitor, cyclopamine, and the activators, Smoothened agonist (SAG) and purmorphamine (PMA). Effectiveness of reagents was assayed using both molecular biological techniques and biological readouts. We found that the small molecule modulators of the Hh pathway were highly specific and effective and produced results generally superior to the more conventional protein reagents for examination of later stage developmental processes.
Hedgehog agonist therapy corrects structural and cognitive deficits in a Down syndrome mouse model. Das I et al. Science translational medicine 2013 SEP

Abstract

Down syndrome (DS) is among the most frequent genetic causes of intellectual disability, and ameliorating this deficit is a major goal in support of people with trisomy 21. The Ts65Dn mouse recapitulates some major brain structural and behavioral phenotypes of DS, including reduced size and cellularity of the cerebellum and learning deficits associated with the hippocampus. We show that a single treatment of newborn mice with the Sonic hedgehog pathway agonist SAG 1.1 (SAG) results in normal cerebellar morphology in adults. Further, SAG treatment at birth rescued phenotypes associated with hippocampal deficits that occur in untreated adult Ts65Dn mice. This treatment resulted in behavioral improvements and normalized performance in the Morris water maze task for learning and memory. SAG treatment also produced physiological effects and partially rescued both N-methyl-d-aspartate (NMDA) receptor-dependent synaptic plasticity and NMDA/AMPA receptor ratio, physiological measures associated with memory. These outcomes confirm an important role for the hedgehog pathway in cerebellar development and raise the possibility for its direct influence in hippocampal function. The positive results from this approach suggest a possible direction for therapeutic intervention to improve cognitive function for this population.
Small molecules greatly improve conversion of human-induced pluripotent stem cells to the neuronal lineage. Mak SK et al. Stem cells international 2012 JAN

Abstract

Efficient in vitro differentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marker expression, reproducibility, length, and cost. Three main neuronal differentiation approaches are stromal-induced neuronal differentiation, embryoid body (EB) differentiation, and direct neuronal differentiation. Here, we describe our neurodifferentiation protocol using small molecules that very efficiently promote neural induction in a 5-stage EB protocol from six induced pluripotent stem cells (iPSC) lines from patients with Parkinson's disease and controls. This protocol generates neural precursors using Dorsomorphin and SB431542 and further maturation into dopaminergic neurons by replacing sonic hedgehog with purmorphamine or smoothened agonist. The advantage of this approach is that all patient-specific iPSC lines tested in this study were successfully and consistently coaxed into the neural lineage.

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