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SAG

Smoothened agonist
 
ALX-270-426-M001 1 mg 289.00 USD
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  • 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.

Product Details

Alternative Name:3-chloro-N-[trans-4-(methylamino)cyclohexyl]-N-[[3-(4-pyridinyl)phenyl]methyl]-benzo[b]thiophene-2-carboxamide
 
Formula:C28H28ClN3OS
 
MW:490.1
 
CAS:912545-86-9
 
Purity:≥95% (HPLC)
 
Identity:Identity determined by MS and NMR.
 
Appearance:White to off-white solid.
 
Solubility:Soluble in DMSO (10mg/ml), sparingly soluble in water (acidification with HCl increases water solubility).
 
Shipping:Ambient Temperature
 
Long Term Storage:-20°C
 
Use/Stability:Stock solutions in DMSO are stable for at least 1 month when stored at -20°C.
 
Regulatory Status:RUO - Research Use Only
 
270-426
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Product Literature References

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;
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;
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;
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;
Plexins promote Hedgehog signaling through their cytoplasmic GAP activity: J.M. Pinskey, et al.; Elife 11, e74750 (2022), Abstract; Full Text
CCRK/CDK20 regulates ciliary retrograde protein trafficking via interacting with BROMI/TBC1D32: T. Noguchi, et al.; PLoS One 16, e0258497 (2021), Abstract;
CEP120-mediated KIAA0753 recruitment onto centrioles is required for timely neuronal differentiation and germinal zone exit in the developing cerebellum: C.H. Chang, et al.; Genes Dev. 35, 1445 (2021), Abstract;
Cooperation of the IFT-A complex with the IFT-B complex is required for ciliary retrograde protein trafficking and GPCR import: T. Kobayashi, et al.; Mol. Biol. Cell 32, 45 (2021), Abstract; Full Text
Directed induction of retinal organoids from human pluripotent stem cells: X. Zhang, et al.; J. Vis. Exp. (2021), Abstract;
Mice lacking DYRK2 exhibit congenital malformations with lung hypoplasia and altered Foxf1 expression gradient: S. Yogosawa, et al.; Commun. Biol. 4, 1204 (2021), Abstract;
Sequences in the stalk domain regulate autoinhibition and ciliary tip localization of the immotile kinesin-4 KIF7: T.L. Blasius, et al.; J. Cell Sci. 134, jcs258464 (2021), Abstract;
Taurine rescues mitochondria-related metabolic impairments in the patient-derived induced pluripotent stem cells and epithelial-mesenchymal transition in the retinal pigment epithelium: K. Homma, et al.; Redox Biol. 41, 101921 (2021), Abstract; Full Text
Patient-specific retinal organoids recapitulate disease features of late-onset retinitis pigmentosa: M.L. Gao, et al.; Front. Cell. Dev. Biol. 8, 128 (2020), Abstract; Full Text
Single-cell transcriptomics of Parkinson's disease human in vitro models reveals dopamine neuron-specific stress responses: H.J.R. Fernandes, et al.; Cell Rep. 33, 108263 (2020), Abstract;
The excretory/secretory Products of Fifth-Stage Larval Angiostrongylus Cantonensis Induces Autophagy via the Sonic Hedgehog Pathway in Mouse Brain Astrocytes: K. Chen, et al.; PLoS Negl. Trop. Dis. 14, e0008290 (2020), Abstract; Full Text
Thyroid hormone-induced expression of Foxl1 in subepithelial fibroblasts correlates with adult stem cell development during Xenopus intestinal remodeling: T. Hasebe, et al.; Sci. Rep. 10, 20715 (2020), Abstract; Full Text
Transient primary cilia mediate robust hedgehog pathway-dependent cell cycle control: E.K. Ho, et al.; Curr. Biol. 30, 2829 (2020), Abstract; Full Text
Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing: F.H. Soddiqi, et al.; Nat. Commun. 10, 1817 (2019), Abstract; Full Text
A novel Cep120-dependent mechanism inhibits centriole maturation in quiescent cells: E. Betleja, et al.; Elife 7, e35439 (2018), Abstract; Full Text
BBSome trains remove activated GPCRs from cilia by enabling passage through the transition zone: F. Ye, et al.; J. Cell Biol. 217, 1847 (2018), Abstract; Full Text
Dynamic remodeling of membrane composition drives cell cycle through primary cilia excision: S.C. Phua, et al.; Cell 148 , 264 (2017), Abstract; Full Text
Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor.: X. Wu, et al.; Nat. Cell Biol. 19, 1226 (2017), Abstract; Full Text
Generation of Xeno-Free, cGMP-Compliant Patient-Specific iPSCs from Skin Biopsy.: L.A. Wiley, et al.; Curr. Protoc. Stem Cell Biol. 42, 4A.12.1 (2017), Abstract; Full Text
Maml1 acts cooperatively with Gli proteins to regulate sonic hedgehog signaling pathway: R. Quaranta, et al.; Cell Death Dis. 7, e2942 (2017), Abstract; Full Text
cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness: L.A. Wiley, et al.; Sci. Rep. 6, 30742 (2016), Abstract; Full Text
Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells: C. Ozone, et al.; Nat. Commun. 7, Article number 10351 (2016), Application(s): Cell culture, Abstract;
Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups: D.A. Parfitt, et al.; Cell Stem Cell 18, 769 (2016), Application(s): Cell culture, Abstract;
Sequential Differentiation of Embryonic Stem Cells into Neural Epithelial-Like Stem Cells and Oligodendrocyte Progenitor Cells: J. Bian, et al.; PLoS One 11, e0155227 (2016), Application(s): Cell culture, Abstract; Full Text
Asymmetric cell division of granule neuron progenitors in the external granule layer of the mouse cerebellum: P. Haldipur, et al.; Biol. Open 4, 865 (2015), Abstract; Full Text
Modeling amyotrophic lateral sclerosis in pure human iPSc-derived motor neurons isolated by a novel FACS double selection technique: D. Toli, et al.; Neurobiol. Dis. 82, 269 (2015), Application(s): Cell Culture, Abstract;
Subregional specification of embryonic stem cell-derived ventral telencephalic tissues by timed and combinatory treatment with extrinsic signals: T. Danjo, et al.; J. Neurosci. 31, 1919 (2011), Abstract;
Identification of a suppressive mechanism for Hedgehog signaling through a novel interaction of Gli with 14-3-3: Y. Asoaka, et al.; J. Biol. Chem. 285, 4185 (2010), Abstract; Full Text
Wnt signaling stimulates transcriptional outcome of the Hedgehog pathway by stabilizing GLI1 mRNA: F.K. Noubissi, et al.; Cancer Res. 69, 8572 (2009), Abstract; Full Text
Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells: R.B. Corcoran and M.P. Scott; PNAS 103, 8408 (2006), Abstract; Full Text
Smoothened Signal Transduction is Promoted by G-Protein Coupled Receptor Kinase 2: A.R. Meloni et al.; Mol Cell Biol. 26, 7550 (2006), Abstract;
Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2: W. Chen, et al.; Science 306, 2257 (2004), Abstract;
Small molecule modulation of Smoothened activity: J.K. Chen, et al.; PNAS 99, 14071 (2002), Abstract; Full Text
Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists: M. Frank-Kamenetsky, et al.; J. Biol. 1, 10 (2002), Abstract; Full Text

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