Art. -Nr.: HY-12848

SAG

44 Cited Publications

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Based on 44 publication(s) in Google Scholar

SAG is a potent Smoothened (Smo) receptor agonist (EC₅₀=3 nM; K_d=59 nM). SAG activates the Hedgehog signaling pathway and counteracts Cyclopamine (HY-17024) inhibition of Smo.

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Reinheit: 99.60%
CAS. Nr.: 912545-86-9
Formel: C₂₈H₂₈ClN₃OS
Molecular Weight:490.06

Speicherung:

4°C, protect from light

* In solvent : -80°C, 2 years; -20°C, 1 year (protect from light)

SAG Chemical Structure

CAS. Nr.: 912545-86-9

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (44)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

SAG is a potent Smoothened (Smo) receptor agonist (EC₅₀=3 nM; K_d=59 nM). SAG activates the Hedgehog signaling pathway and counteracts Cyclopamine (HY-17024) inhibition of Smo^[1]^[2]^[3].

IC₅₀ & Target

EC50: 3 nM (Smo)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
C3H 10T1/2	EC₅₀	0.13 μM Compound: SAG	Agonist activity at Smo in mouse C3H10T1/2 cells assessed as induction of cell differentiation into osteoblast incubated for 6 days by alkaline phosphatase assay Agonist activity at Smo in mouse C3H10T1/2 cells assessed as induction of cell differentiation into osteoblast incubated for 6 days by alkaline phosphatase assay	[PMID: 27429255]
HUVEC	IC₅₀	22 μM Compound: 10a	Cytotoxicity against HUVEC after 24 hrs by WST-1 assay Cytotoxicity against HUVEC after 24 hrs by WST-1 assay	[PMID: 22985958]
Shh Light II	EC₅₀	8.8 nM Compound: 10a	Activation of Shh pathway in mouse Shh-Light II cells assessed as induction of gli1 expression after 48 hrs by renilla luminescence assay Activation of Shh pathway in mouse Shh-Light II cells assessed as induction of gli1 expression after 48 hrs by renilla luminescence assay	[PMID: 22985958]

In Vitro

SAG (0.1 nM-100 μM; 30 h) induces firefly luciferase expression in Shh-LIGHT2 cells with an EC₅₀ of 3 nM and then inhibits expression at higher concentrations^[1].
SAG (1-1000 nM; 1 h) competes for the binding of BODIPY-cyclopamine to Smo-expressing Cos-1 cells, yielding an apparent dissociation constant (K_d) of 59 nM for the SAG/Smo complex^[1].
SAG (100 nM) inhibits the inhibitory effect of ShhN-induced pathway activation by Robotnikinin^[2].
SAG (250 nM; 48 h) significantly increases SMO mRNA and protein expression in MDAMB231 cells^[3].
SAG (250 nM; 24 and 48 h) increases CAXII mRNA expression in MDAMB231 cells at 24h in normoxic and hypoxic conditions in MDAMB231 cells^[3].
SAG (250 nM; 24 h) increases MDAMB231 cells migration^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

SAG (1.0 mM) induces more osteogenesis mainly at the defect borders and a significant increase in BV/TV at the eight-week timepoint in CD-1 mice^[4].
SAG (15-20 mg/kg; i.p.) induces pre-axial polydactyly prevalently in a dose-dependent manner in mice^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Pregnant C57BL/6J mice^[5]
Dosage:

15, 17, 20 mg/kg
Administration:

A single i.p.
Result:

Effective in ca. 80% of the embryos and increased Gli1 and Gli2 mRNA expression in the limb bud, with Gli1 mRNA being the most upregulated at the dose of 20 mg/kg.

Chemical Information

CAS. Nr. 912545-86-9
Appearance Solid
Molecular Weight 490.06
Formel C₂₈H₂₈ClN₃OS
Color White to yellow
SMILES

O=C(C1=C(Cl)C2=CC=CC=C2S1)N([C@H]3CC[C@H](NC)CC3)CC4=CC=CC(C5=CC=NC=C5)=C4
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

4°C, protect from light

* In solvent : -80°C, 2 years; -20°C, 1 year (protect from light)

Publications (44)

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Journal Impact Factor

Cell Res

Cholesterylation of Smoothened is a calcium-accelerated autoreaction involving an intramolecular ester intermediate. [Abstract]

2022 Mar;32(3):288-301. PMID: 35121857

SAG purchased from MedChemExpress. Usage Cited in: Cell Res. 2022 Mar;32(3):288-301. [Abstract]

SAG (5-200 nM)-induced Gli1 expression is independent of extracellular Ca²⁺ concentration. Sub-confluent NIH3T3 cells were serum-starved in 0.5% FCS overnight and switched to normal DMEM or Ca²⁺-free DMEM containing indicated concentration of SAG. Cells were harvested for RNA extraction after 6 hours.
Cell Stem Cell

Establishing dorsal-ventral patterning in human neural tube organoids with synthetic organizers. [Abstract]

2025 Jul 3;32(7):1071-1086.e8. PMID: 40373768
Nat Commun

Identification of a component of the tubulin poly-glutamylase complex required for phosphoinositide homeostasis and cilium assembly and maintenance. [Abstract]

2026 May 15. PMID: 42140944
Nat Commun

Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma. [Abstract]

2024 Feb 2;15(1):987. PMID: 38307877
Adv Sci (Weinh)

Primary Cilia Formation Mediated by Hsa_Circ_0005185/OTUB1/RAB8A Complex Inhibits Prostate Cancer Progression by Suppressing Hedgehog Signaling Pathway. [Abstract]

2025 Jan 9:e2411675. PMID: 39785769
Sci Adv

Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells. [Abstract]

2025 Jan 10;11(2):eads5434. PMID: 39792663
Sci Adv

Yap controls notochord formation and neural tube patterning by integrating mechanotransduction with FoxA2 and Shh expression. [Abstract]

2023 Jun 16;9(24):eadf6927. PMID: 37315133

SAG purchased from MedChemExpress. Usage Cited in: Sci Adv. 2023 Jun 16;9(24):eadf6927. [Abstract]

Representative immunofluorescent images of TdTomato (tdTom) and brachyury (T) at E10.5 in trunk cross sections of indicated genotypes with or without small molecule agonist (SAG, 20 mg/kg; i.p.) treatment. Scale bar, 100 μm.
Cell Commun Signal

TGFβ1-induced hedgehog signaling suppresses the immune response of brain microvascular endothelial cells elicited by meningitic Escherichia coli. [Abstract]

2024 Feb 15;22(1):123. PMID: 38360663

SAG purchased from MedChemExpress. Usage Cited in: Cell Commun Signal. 2024 Feb 15;22(1):123. [Abstract]

qPCR detecting expression alterations of IL-6, MIP-2, and E-selectin in RS218 infected hBMECs with or without SAG pre-treatment (at 10 μM).

SAG purchased from MedChemExpress. Usage Cited in: Cell Commun Signal. 2024 Feb 15;22(1):123. [Abstract]

Western blot detecting expression of E-selectin, KRAS and ERK1/2 phosphorylation in RS218 infected hBMECs with or without SAG pre-treatment (at 10 μM).

SAG purchased from MedChemExpress. Usage Cited in: Cell Commun Signal. 2024 Feb 15;22(1):123. [Abstract]

IF assays showing the E-selectin and KRAS expression in brains of mice challenged by RS218 with or without SAG (10 mg/kg, i.v.; single dose) pre-treatment. The E-selection and KRAS were stained in red. CD31 was specifically applied for labeling the micro-vessels in green. The cell nucleus was stained in blue with DAPI. Scale bar = 50 μm
Cell Mol Gastroenterol Hepatol

Triggering Receptor Expressed on Myeloid Cells 2+ Macrophages Promote Pancreatic Regeneration Through Cholesterol-Metabolism Reprogramming and Hedgehog Signaling Activation Following Acute Pancreatitis. [Abstract]

2026 May 27:101819. PMID: 42208763
Cell Rep

2020 Apr.
Biomater Adv

A supramolecular MgTA@MnO₂ nanozyme platform supports human spinal cord organoid structural integration and locomotor recovery via microenvironmental reprogramming. [Abstract]

2026 Jun 16:188:215018. PMID: 42309040
Ecotoxicol Environ Saf

Zearalenone at environmental levels promoted ER- positive breast cancer cell lines through the hedgehog pathway. [Abstract]

2025 Aug 6:303:118813. PMID: 40773915
Biochem Pharmacol

Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma. [Abstract]

2021 Aug:190:114593. PMID: 33964282
Cell Rep Methods

Effective cryopreservation of human brain tissue and neural organoids. [Abstract]

2024 May 8:100777. PMID: 38744289
Glia

RXR Gamma Enables Oligodendrocyte Differentiation by Suppressing Sonic Hedgehog Signaling. [Abstract]

2026 Jun;74(6):e70151. PMID: 41934103
Glia

Deubiquitinase USP18 regulates reactive astrogliosis by stabilizing SOX9. [Abstract]

2021 Jul;69(7):1782-1798. PMID: 33694203
J Pathol

Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of Ménétrier's disease. [Abstract]

2025 Nov 6. PMID: 41199529
Molecules

Synthesis and Smo Activity of Some Novel Benzamide Derivatives. [Abstract]

2017 Dec 31;23(1). pii: E85. PMID: 29301237
Sci Rep

Tanshinone IIA inhibits foam cell formation and alleviates atherosclerosis by regulating the Hedgehog signaling pathway through TRPM2 suppression. [Abstract]

2026 May 18. PMID: 42151241
Sci Rep

Ptbp1 knockdown induces conversion of rat spinal cord astrocytes into neuron like cells. [Abstract]

2025 Oct 14;15(1):35928. PMID: 41087401
Cancer Sci

Transcription factor POU4F2 promotes colorectal cancer cell migration and invasion through hedgehog-mediated epithelial-mesenchymal transition. [Abstract]

2021 Oct;112(10):4176-4186. PMID: 34327778
J Cell Mol Med

Whole-exome sequencing identified novel variants in CPLANE1 that causes oral-facial-digital syndrome Ⅵ by inducing primary cilia abnormality. [Abstract]

2022 Jun;26(11):3213-3222. PMID: 35582950
Biomedicines

Generation of a Pure Culture of Neuron-like Cells with a Glutamatergic Phenotype from Mouse Astrocytes. [Abstract]

2022 Apr 18;10(4):928. PMID: 35453678
iScience

Modeling the precise interaction of glioblastoma with human brain region-specific organoids. [Abstract]

2024 Feb 5;27(3):109111. PMID: 38390494
iScience

Generation of dorsoventral human spinal cord organoids via functionalizing composite scaffold for drug testing. [Abstract]

2022 Dec 26;26(1):105898. PMID: 36647382
Drug Dev Res

Curcumin mitigates the epithelial-to-mesenchymal transition in biliary epithelial cells through upregulating CD109 expression. [Abstract]

2019 Nov;80(7):992-999. PMID: 31403228
Toxins

Human-Relevant Sensitivity of iPSC-Derived Human Motor Neurons to BoNT/A1 and B1. [Abstract]

2021 Aug 22;13(8):585. PMID: 34437455
Development

Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling. [Abstract]

2018 Sep 20;145(18). pii: dev164830. PMID: 30111653

SAG purchased from MedChemExpress. Usage Cited in: Development. 2018 Sep 20;145(18). pii: dev164830. [Abstract]

WT MEF cells are treated with 100 nM SAG, 0.1mM ATP, or 0.1mM NHATP for 10 min (U). p-Creb, total Creb and Tubulin protein levels are detected by Western blotting.
J Tradit Complement Med

2025 Jun 14.
J Biomed Mater Res A

GelMA Hydrogel Encapsulating iPSC-Derived Human Spinal Cord Organoids Enhances Neural Regeneration and Restores Motor Function in Rat Spinal Cord Injury. [Abstract]

2025 Oct;113(10):e38001. PMID: 41051068
Mol Brain

Meningitic Escherichia coli α-hemolysin aggravates blood-brain barrier disruption via targeting TGFβ1-triggered hedgehog signaling. [Abstract]

2021 Jul 19;14(1):116. PMID: 34281571
J Pharm Biomed Anal

Rapid discovery of cyclopamine analogs from Fritillaria and Veratrum plants using LC-Q-TOF-MS and LC-QqQ-MS. [Abstract]

2017 Aug 5:142:201-209. PMID: 28521273
Neuroscience

Trichostatin A-primed spinal cord organoids alleviate oxidative stress and improve recovery after spinal cord injury involving the NRF2/HO-1 signaling pathway. [Abstract]

2026 Jun 6:610:122-135. PMID: 42250855
Exp Eye Res

The effects of pigment epithelium-derived factor and associated peptides on the differentiation of retinal ganglion cells from human-induced pluripotent stem cells. [Abstract]

2025 May 21:110440. PMID: 40409357
Tissue Cell

The Shh-p38-NFATc1 signaling pathway is essential for osteoclastogenesis during tooth eruption. [Abstract]

2024 Nov 28:92:102643. PMID: 39612595
bioRxiv

Rapid Remodeling of Human White Adipose Tissue Following Bariatric Surgery. [Abstract]

2026 Apr 15:2026.04.09.717542. PMID: 42039637
bioRxiv

Neuronal Cell-Cycle Re-entry Defines Divergent Outcomes Through Replication-Dependent DNA Damage in ALS. [Abstract]

2026 Feb 16:2026.02.13.705790. PMID: 41756973
Res Sq

2026 Feb 2.
bioRxiv

2025 July 21.
bioRxiv

2025 March 25.
Patent

US20240247230A1.
UNIVERSIDAD DE CONCEPCIÓN

2023 Apr.
Research Square Preprint

2021 Sep.
University of Bonn

2021 May 21.

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (204.06 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.0406 mL

10.2028 mL

20.4057 mL

5 mM

0.4081 mL

2.0406 mL

4.0811 mL

10 mM

0.2041 mL

1.0203 mL

2.0406 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (protect from light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 5 mg/mL (10.20 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 5 mg/mL (10.20 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 5 mg/mL (10.20 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (277 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Chen JK, et al. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6. [Content Brief]

[2]. Stanton BZ, et al. A small molecule that binds Hedgehog and blocks its signaling in human cells. Nat Chem Biol. 2009 Mar;5(3):154-6. [Content Brief]

[3]. Guerrini G, et, al. Inhibition of smoothened in breast cancer cells reduces CAXII expression and cell migration. J Cell Physiol. 2018 Dec; 233(12): 9799-9811. [Content Brief]

[4]. Lee S, et al. Combining Smoothened Agonist (SAG) and NEL-like protein-1 (NELL-1) Enhances Bone Healing. Plast Reconstr Surg. 2017 Feb 13 [Content Brief]

[5]. Fish EW, et al. Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice. Birth Defects Res A Clin Mol Teratol. 2016 Nov 1 [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.0406 mL	10.2028 mL	20.4057 mL	51.0142 mL
	5 mM	0.4081 mL	2.0406 mL	4.0811 mL	10.2028 mL
	10 mM	0.2041 mL	1.0203 mL	2.0406 mL	5.1014 mL
	15 mM	0.1360 mL	0.6802 mL	1.3604 mL	3.4009 mL
	20 mM	0.1020 mL	0.5101 mL	1.0203 mL	2.5507 mL
	25 mM	0.0816 mL	0.4081 mL	0.8162 mL	2.0406 mL
	30 mM	0.0680 mL	0.3401 mL	0.6802 mL	1.7005 mL
	40 mM	0.0510 mL	0.2551 mL	0.5101 mL	1.2754 mL
	50 mM	0.0408 mL	0.2041 mL	0.4081 mL	1.0203 mL
	60 mM	0.0340 mL	0.1700 mL	0.3401 mL	0.8502 mL
	80 mM	0.0255 mL	0.1275 mL	0.2551 mL	0.6377 mL
	100 mM	0.0204 mL	0.1020 mL	0.2041 mL	0.5101 mL

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SAG

Stem Cell Signaling Compound Library

Wnt/Hedgehog/Notch Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Reprogramming Compound Library

Anti-Pancreatic Cancer Compound Library

Targeted Diversity Library

Heterocyclic Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Publications Citing Use of MedChemExpress (MCE) SAG

Biologische Aktivität

Chemical Information

Publications (44)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

SAG

Stem Cell Signaling Compound Library

Wnt/Hedgehog/Notch Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Reprogramming Compound Library

Anti-Pancreatic Cancer Compound Library

Targeted Diversity Library

Heterocyclic Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Publications Citing Use of MedChemExpress (MCE) SAG

Biologische Aktivität

Chemical Information

Publications (44)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

SAG Related Classifications

HY-12848 Related Classifications