GSA 10

Hedgehog pathway activator; Activates Smoothened (SMO)
Catalog #
73172_C
Hedgehog pathway activator; Activates Smoothened (SMO)
From: 975 USD

Overview

GSA 10 is an agonist of Smoothened (SMO), a cell surface receptor and mediator of the hedgehog signaling pathway. It is a quinolinecarboxamide derivative that binds in a distinct binding pocket from cyclopamine. GSA10 is active at an EC₅₀ of 1.2 μM in an alkaline phosphatase-based mouse mesenchymal cell line (C3H10T1/2) differentiation assay (Gorojankina et al.).

DIFFERENTIATION
· Promotes differentiation of multipotent mesenchymal progenitor cells into osteoblasts (Gorojankina et al.).
Alternative Names
Not applicable
Cell Type
Mesenchymal Stem and Progenitor Cells, Osteoblasts
Species
Human, Mouse, Rat, Non-Human Primate, Other
Application
Differentiation
Area of Interest
Stem Cell Biology
CAS Number
300833-95-8
Chemical Formula
C₂₆H₃₀N₂O₅
Molecular Weight
450.5 g/mol
Purity
≥ 95%
Pathway
Hedgehog
Target
SMO

Scientific Resources

Product Documentation

Document Type Product Name Catalog # Lot # Language
Document Type
Product Information Sheet
Product Name
GSA 10
Catalog #
73174
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
GSA 10
Catalog #
73174
Lot #
All
Language
English

Educational Materials (3)

Wallchart
Small Molecules, Big Impact in Pluripotent Stem Cell Research
Wallchart
Small Molecules, Big Impact in Cancer Research
Mini Review
Small Molecules

Product 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.

Data and Publications

Publications (1)

Molecular pharmacology 2013 Discovery, molecular and pharmacological characterization of GSA-10, a novel small-molecule positive modulator of Smoothened. Gorojankina T et al.

Abstract

Activation of the Smoothened (Smo) receptor mediates Hedgehog (Hh) signaling. Hh inhibitors are in clinical trials for cancer, and small-molecule Smo agonists may have therapeutic interests in regenerative medicine. Here, we have generated and validated a pharmacophoric model for Smo agonists and used this model for the virtual screening of a library of commercially available compounds. Among the 20 top-scoring ligands, we have identified and characterized a novel quinolinecarboxamide derivative, propyl 4-(1-hexyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamido) benzoate, (GSA-10), as a Smo agonist. GSA-10 fits to the agonist pharmacophoric model with two hydrogen bond acceptor groups and four hydrophobic regions. Using pharmacological, biochemical, and molecular approaches, we provide compelling evidence that GSA-10 acts at Smo to promote the differentiation of multipotent mesenchymal progenitor cells into osteoblasts. However, this molecule does not display the hallmarks of reference Smo agonists. Remarkably, GSA-10 does not recognize the classic bodipy-cyclopamine binding site. Its effect on cell differentiation is inhibited by Smo antagonists, such as MRT-83, SANT-1, LDE225, and M25 in the nanomolar range, by GDC-0449 in the micromolar range, but not by cyclopamine and CUR61414. Thus, GSA-10 allows the pharmacological characterization of a novel Smo active site, which is notably not targeted to the primary cilium and strongly potentiated by forskolin and cholera toxin. GSA-10 belongs to a new class of Smo agonists and will be helpful for dissecting Hh mechanism of action, with important implications in physiology and in therapy.
View All Publications

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