Smoothened Agonist (SAG) HCl

Catalog No.S7779

Smoothened Agonist (SAG) HCl Chemical Structure

Molecular Weight(MW): 526.52

Smoothened Agonist (SAG) HCl is a cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells.

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Cited by 5 Publications

1 Customer Review

  • Activating Shh signaling by SAG injection in naïve mice significantly increased BDNF expression, and pretreatment with cyclopamine effectively prevented the upregulation of BDNF induced by SAG (E). Tissues were collected at 2 hours after SAG injection. Six mice were included in each group.

    J Pain Res, 2018, 11:649-659. Smoothened Agonist (SAG) HCl purchased from Selleck.

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Biological Activity

Description Smoothened Agonist (SAG) HCl is a cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells.
Targets
Smoothened [1]
(mouse cultured cell assay)
3 nM(EC50)
In vitro

SAG regulates Smo activity by binding directly to the Smo heptahelical bundle. [1] SAG induces Smo-dependent signaling through Gli in a GRK2-dependent way. [2] SAG also (1 nM) induces proliferation of neuronal and glial precursors without affecting the differentiation pattern of newly produced cells. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mouse Shh-Light II cell MYjGeY5kfGmxbjDhd5NigQ>? NEXlb2k1QCCqcoO= NVHOfGVoSWO2aY\heIlwdiCxZjDTbIgheGG2aIfhfUBqdiCvb4Xz[UBUcGhvTHnnbJQhUUliY3XscJMh[XO|ZYPz[YQh[XNiaX7keYN1cW:wIH;mJIdtcTFiZYjwdoV{e2mxbjDh[pRmeiB2ODDodpMh[nlicnXubYxt[SCudX3pcoV{[2WwY3WgZZN{[XluIFXDOVA:OC5yMEi4JO69VQ>? MWOyNlk5PTl3OB?=
HUVEC MVnDfZRwfG:6aXPpeJkh[XO|YYm= M1nOOVI1KGh? MULDfZRwfG:6aXPpeJkh[WejaX7zeEBJXV[HQzDh[pRmeiB{NDDodpMh[nliV2PUMVEh[XO|YYmsJGlEPTB;MkKg{txO NWjlPWlMOjJ7OEW5OVg>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
LC3I / LC3II; 

PubMed: 23504944     


Western blotting for LC3I/II. Huh7, Hep3B and HepG2 cells were incubated with vehicle control, SAG (0.5 µM), Pur (10 µM), Shh (0.4 µg/ml), GANT61 (20 µM) or GDC0449 (20 µM) for 48 hours.

23504944
Immunofluorescence
Smo; 

PubMed: 25636740     


In the absence of SAG, Smo is not detected at the cilium. MRT-92 alone does not induce Smo trafficking to the primary cilium. Cell exposure to SAG induces Smo trafficking to the cilium, which is abolished by MRT-92.

acetylated alpha tubulin; 

PubMed: 25992706     


TM3 cells were cultured in the presence of the SMO agonist (SAG) to monitor response to HH activation. A) In control cells (a-c; 0 h), primary cilia marked by Ac-T (red; arrows) only displayed occasional, speckled appearance of SMO (green). After 1 h in the presence of 100 nM SAG (d-f), a stronger and more frequent localization of SMO to the primary cilia was observed, now also at the ciliary base (f; insert; arrow), and this was even more apparent after 4 h of SAG-stimulation (g-i). Nuceli were stained with DAPI. Scale bar = 10 μm. 

25636740 25992706
In vivo In the adult rat hippocampus, the intracerebroventricular administration of SAG (2.5 nM) significantly increases the number of newly generated cells and extends survival of hippocampal cells. [3] In mice, SAG (20 μg/g, i.p.) effectively prevents GC-induced neonatal cerebellar developmental abnormalities. [4]

Protocol

Animal Research:[3]
+ Expand
  • Animal Models: Rat
  • Formulation: DMSO
  • Dosages: 2.5 nM
  • Administration: Intracerebroventricular administration
    (Only for Reference)

Solubility (25°C)

In vitro Water 100 mg/mL (189.92 mM)
DMSO 71 mg/mL warmed (134.84 mM)
Ethanol 40 mg/mL warmed (75.97 mM)
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
water
For best results, use promptly after mixing.
100mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 526.52
Formula

C28H29Cl2N3OS

CAS No. 912545-86-9(free base)
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03517943 Completed Clinical Pharmacology Bayer April 24 2018 Phase 1
NCT03517930 Completed Clinical Pharmacology Bayer April 17 2018 Phase 1
NCT03517943 Completed Clinical Pharmacology Bayer April 24 2018 Phase 1
NCT03517930 Completed Clinical Pharmacology Bayer April 17 2018 Phase 1
NCT00990574 Withdrawn Hypotension|Headache Stanford University October 2009 Not Applicable
NCT00990574 Withdrawn Hypotension|Headache Stanford University October 2009 Not Applicable

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Hedgehog/Smoothened Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID