SAG

ALX-270-426

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Smoothened agonist

Potent Smoothened (Smo) receptor agonist
Binds directly to Smo and antagonizes Cyclopamine
Enhancer of neuronal differentiation of iPSCs into dopaminergic neurons

Smoothened (Smo) is a transmembrane receptor that relays the Hedgehog (Hh) signal and plays an essential role during embryonic development and tumorigenesis. SAG is a potent cell-permeable benzothiophene compound that modulates the coupling of Smo with its downstream effector by interacting with the Smo heptahelical domain (KD = 59 nM). SAG was shown to induce Hedgehog pathway activation independently of the Hh binding receptor Patched (Ptch) (EC50= ~3 nM in NIH 3T3-derived Shh-LIGHT2 cells) and counteract inhibition of Smo by Cyclopamine (Prod. No. BML-GR334). Smo is reported to act as an activator at low concentrations and as an inhibitor at very high concentrations.

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Product Details

Alternative Name	3-chloro-N-[trans-4-(methylamino)cyclohexyl]-N-[[3-(4-pyridinyl)phenyl]methyl]-benzo[b]thiophene-2-carboxamide
Appearance	Clear thin film (lyophilized).
CAS	912545-86-9
Couple Target	Smoothened
Couple Type	Activator, Ligand
Formula	C₂₈H₂₈ClN₃OS
Identity	Identity determined by MS and NMR.
MW	490.1
Purity	≥95% (HPLC)
Solubility	Soluble in DMSO (10mg/ml), sparingly soluble in water (acidification with HCl increases water solubility).

Handling & Storage

Use/Stability	As indicated on product label or CoA when stored as recommended. Stock solutions in DMSO are stable for at least 1 month when stored at -20°C.
Long Term Storage	-20°C
Shipping	Ambient Temperature

Regulatory Status	RUO – Research Use Only

CETSA-MS unveils novel targets engaged by rigosertib to promote anti-tumor activity and inflammatory responses: Kechagioglou, P., Yurugi, H., et al.; iScience 28, 112748 (2025), Abstract
Dual and opposing roles for the kinesin-2 motor, KIF17, in Hedgehog-dependent cerebellar development: Waas, B., Carpenter, B. S., et al.; Sci. Adv. 10, eade1650 (2024), Abstract
Semaphorin Receptors Antagonize Wnt Signaling Through Beta-Catenin Degradation: Hoard, T. M., Liu, K., et al.; bioRxiv , (2024)
CRX haploinsufficiency compromises photoreceptor precursor translocation and differentiation in human retinal organoids: D. Pan, et al.; Stem Cell Res. Ther. 14, 346 (2023), Abstract
Generation of 3D lung organoids from human induced pluripotent stem cells for modeling of lung development and viral infection: Tiwari, S. K., Rana, T. M., et al.; Heliyon 9, e19601 (2023), Abstract
Hedgehog-induced ciliary trafficking of kinesin-4 motor KIF7 requires intraflagellar transport but not KIF7’s microtubule binding: Y. Yue, et al.; Mol. Biol. Cell 33, br1 (2022), Abstract
Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling: M. Maimets, et al.; Nat. Commun. 13, 715 (2022), Abstract
Molecular basis underlying the ciliary defects caused by IFT52 variations found in skeletal ciliopathies: Y. Ishida, et al.; Mol. Biol. Cell 33, ar83 (2022), Abstract
Hoxb1 regulates distinct signaling pathways in neuromesodermal and hindbrain progenitors to promote cell survival and specification: K. Pazur, et al.; Stem Cells 40, 175 (2022), Abstract
Pituitary Lineage Differentiation from Human Induced Pluripotent Stem Cells in 2D and 3D Cultures: Y. Zhou, et al.; Stem Cells Dev. 31, 239 (2022), Abstract

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Last modified: May 29, 2024

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SAG

ALX-270-426

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