INT-777 (Synonyms: S-EMCA)

Name: INT-777
Brand: MedChemExpress
SKU: HY-15677
Rating: 5.0 (42 reviews)

Cat. No.: HY-15677 Purity: ≥98.0%: FAQs
Data Sheet SDS COA Handling Instructions

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INT-777 is a potent TGR5 agonist with an EC₅₀ of 0.82 μM.

For research use only. We do not sell to patients.

INT-777 Chemical Structure

CAS No. : 1199796-29-6

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 462	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 462	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 420	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 600	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 1350	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 1880	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 42 publication(s) in Google Scholar

Other Forms of INT-777:

INT-777 (R-enantiomer) In-stock

35 Publications Citing Use of MCE INT-777

IHC

: INT-777 purchased from MedChemExpress. Usage Cited in: J Am Soc Nephrol. 2018 Nov;29(11):2658-2670. [Abstract]; Western blots show that INT-767, INT-777, and INT747 upregulate AQP2 protein expression.

: INT-777 purchased from MedChemExpress. Usage Cited in: Front Immunol. 2018 Oct 2;9:2289. [Abstract]; Immunoblot analysis of p-IRF3 and p-AKT in lysates of peritoneal macrophages (PEMs) pretreated with MK2206 (3 μM) or INT-777 (500 μM) for 1 h, and then infected with vesicular stomatitis virus (VSV) for 8 h.

: INT-777 purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2018 Sep 3;503(1):38-44. [Abstract]; Western Blot analysis of RIP3, and p-MLKL protein expressions detected in pancreatic tissues with the treatment of AP or AP plus INT-777.

: INT-777 purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2018 Sep 3;503(1):38-44. [Abstract]; Representative immunohistochemistry images for RIP3 expression in the pancreas with the treatment of AP or AP plus INT-777.

: INT-777 purchased from MedChemExpress. Usage Cited in: Chinese Journal of Pathophysiology. 2017, 33(2):239-243.; The effects of TGR5 activation on the mRNA (A) and protein (B) expression of CaN in the mouse cardiomyocytes induced by high glucose (HG).

: INT-777 purchased from MedChemExpress. Usage Cited in: Immunity. 2016 Oct 18;45(4):944. [Abstract]; INT-777, a semi-synthetic TGR5 agonist, markedly represses caspase-1 maturation and IL-1β or IL-18 but not the TNF-α secretion induced by Nigericin, similar to LCA. LPS-primed BMDMs are treated with different doses of INT-777 and then stimulated with Nigericin. Supernatants (SN) and cell extracts (Lysate) are analyzed by immunoblotting.

: INT-777 purchased from MedChemExpress. Usage Cited in: Endocrine. 2016 Dec;54(3):657-670. [Abstract]; After the transfection, the GMCs are treated with 10 μM INT-777 or DMSO (control) upon HG stimulation for 24 h. Western blot is performed to measure the protein expressions of FN and TGF-β. Upon HG stimulation, INT-777 treatment alone can significantly reduce the FN and TGF-β1 protein expressions, and the effect is potentiated by TGR5 overexpression.

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Biological Activity
Protocol
Purity & Documentation
References
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Description

INT-777 is a potent TGR5 agonist with an EC₅₀ of 0.82 μM^[1].

IC₅₀ & Target

EC50: 0.82 μM (TGR5)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	EC₅₀	3.44 μM Compound: 8, S-EMCA, INT-777	Agonist activity at human TGR5 expressed in CHO cells assessed as increase in CRE-driven gene expression by luciferase reporter gene assay Agonist activity at human TGR5 expressed in CHO cells assessed as increase in CRE-driven gene expression by luciferase reporter gene assay	[PMID: 20014870]
COS-1	EC₅₀	> 100 μM Compound: 8, S-EMCA, INT-777	Agonist activity at FXR expressed in COS1 cells by cell-based bioluminescence assay Agonist activity at FXR expressed in COS1 cells by cell-based bioluminescence assay	[PMID: 20014870]
HEK293	EC₅₀	0.36 μM Compound: 1, INT-777, S-EMCA	Agonist activity at mouse TGR5 expressed in HEK293 cells assessed CRE-induced luciferase activity after 5.5 hrs by reporter gene assay Agonist activity at mouse TGR5 expressed in HEK293 cells assessed CRE-induced luciferase activity after 5.5 hrs by reporter gene assay	[PMID: 24007860]
HEK293	EC₅₀	1.23 μM Compound: 1, INT-777, S-EMCA	Agonist activity at human TGR5 expressed in HEK293 cells assessed CRE-induced luciferase activity after 5.5 hrs by reporter gene assay Agonist activity at human TGR5 expressed in HEK293 cells assessed CRE-induced luciferase activity after 5.5 hrs by reporter gene assay	[PMID: 24007860]
HEK293	EC₅₀	293 nM Compound: INT-777	Agonist activity at human TGR5 expressed in HEK293 cells assessed as cAMP level after 48 hrs by fluorescent assay Agonist activity at human TGR5 expressed in HEK293 cells assessed as cAMP level after 48 hrs by fluorescent assay	[PMID: 25082126]
NCI-H716	EC₅₀	0.82 μM Compound: 3, INT-777, S-EMCA	Agonist activity at TGR5 expressed in NCI-H716 cells assessed as cAMP level after 60 mins by FRET analysis Agonist activity at TGR5 expressed in NCI-H716 cells assessed as cAMP level after 60 mins by FRET analysis	[PMID: 24900463]

In Vitro

INT-777 is a novel potent and selective TGR5 agonist with remarkable in vivo activity^[1]. INT-777 (3 μM) increases ATP production in the human enteroendocrine cell line NCI-H716 in a cAMP-dependent manner^[2]. INT-777 (10 μM) lowers Isc and increases TEER when added on the serosal side of seromuscular stripped distal colon segments. INT-777 effect on basal secretion is reduced in neuron-free and TTX-treated mucosal-submucosal preparations^[3].

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

In Vivo

INT-777 (1 μM/min/kg, p.o.) has a potent choleretic effect, prevents carboxyl CoA activation and subsequent conjugation, thereby favoring its chole-hepatic shunt pathway with a ductular absorption and a potent choleretic effect in HF-fed TGR5-Tg male mice^[1]. INT-777 (30 mg/kg/day, p.o.) increases energy expenditure and reduces hepatic steatosis and obesity upon high-fat feeding in TGR5-Tg mice^[2].

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

Molecular Weight

450.65

Formula

C₂₇H₄₆O₅

CAS No.

1199796-29-6

Appearance

Solid

Color

White to yellow

SMILES

O[C@@H]1CC[C@@]2(C)[C@@]([C@@H](CC)[C@@H](O)[C@]3([H])[C@]2([H])C[C@H](O)[C@@]4(C)[C@@]3([H])CC[C@@H]4[C@H](C)C[C@H](C)C(O)=O)([H])C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

Ethanol : ≥ 50 mg/mL (110.95 mM)

DMSO : ≥ 31 mg/mL (68.79 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.2190 mL	11.0951 mL	22.1902 mL
5 mM	0.4438 mL	2.2190 mL	4.4380 mL
10 mM	0.2219 mL	1.1095 mL	2.2190 mL

View the Complete Stock Solution Preparation Table

* 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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator
Dilution Calculator

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

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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

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% EtOH 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.55 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 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.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% EtOH 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.55 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% EtOH 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.55 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 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 EtOH stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
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: 0.5% CMC-Na/saline water
Solubility: 5 mg/mL (11.10 mM); Suspension solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

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

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 100.0%

Select Batch:

Data Sheet (281 KB) SDS (251 KB)

COA (251 KB) HNMR (182 KB) LCMS (295 KB)

Handling Instructions (2659 KB)

References

[1]. Pellicciari R, et al. Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity. J Med Chem. 2009 Dec 24;52(24):7958-61. [Content Brief]

[2]. Thomas C, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009 Sep;10(3):167-77. [Content Brief]

[3]. Duboc H, et al.Reduction of epithelial secretion in male rat distal colonic mucosa by bile acid receptor TGR5 agonist, INT-777: role of submucosal neurons. Neurogastroenterol Motil. 2016 Jun 3. doi: 10.1111/nmo. [Content Brief]

[4]. Baiqiang Li, et al. INT-777, a bile acid receptor agonist, extenuates pancreatic acinar cells necrosis in a mouse model of acute pancreatitis. Biochem Biophys Res Commun. 2018 Sep 3;503(1):38-44. [Content Brief]

Cell Assay ^[2]	The experiments are carried out in STC-1 or NCI-H716 cells treated with vehicle (DMSO) or INT-777. INT-777 is assessed for its agonistic activity on TGR5. cAMP production is performed. Cytochrome C oxidase activity is evaluated by following the oxidation of fully reduced cytochrome C at 550 nm. ATP/ADP ratio and GLP-1 release is measured according to the manufacturer's instruction. Primary brown adipocytes are prepared and ileal explants are prepared. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[2]	Age-matched male mice are used for all experiments. Genetically engineered mouse models (GEMMs), i.e. TGR5-Tg and TGR5-/- mice are generated. Diet-induced obesity (DIO) in the GEMMs or C57BL/6J mice is induced by feeding 8-week-old mice with a HF-diet (60%Cal/fat, D12492) for at least 8 weeks, as mentioned in the text and figure legends. In the dietary intervention experiments, INT-777 is mixed with diet at the dose sufficient to reach an in vivo dose of 30mg/kg/d. Mouse phenotyping experiments are performed according to EMPRESS protocols and aimed to assess food and water intake, body composition, energy expenditure, glucose and lipid homeostasis, and plasma biochemistry. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Pellicciari R, et al. Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity. J Med Chem. 2009 Dec 24;52(24):7958-61. [Content Brief] [2]. Thomas C, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009 Sep;10(3):167-77. [Content Brief] [3]. Duboc H, et al.Reduction of epithelial secretion in male rat distal colonic mucosa by bile acid receptor TGR5 agonist, INT-777: role of submucosal neurons. Neurogastroenterol Motil. 2016 Jun 3. doi: 10.1111/nmo. [Content Brief] [4]. Baiqiang Li, et al. INT-777, a bile acid receptor agonist, extenuates pancreatic acinar cells necrosis in a mouse model of acute pancreatitis. Biochem Biophys Res Commun. 2018 Sep 3;503(1):38-44. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO / Ethanol	1 mM	2.2190 mL	11.0951 mL	22.1902 mL	55.4754 mL
	5 mM	0.4438 mL	2.2190 mL	4.4380 mL	11.0951 mL
	10 mM	0.2219 mL	1.1095 mL	2.2190 mL	5.5475 mL
	15 mM	0.1479 mL	0.7397 mL	1.4793 mL	3.6984 mL
	20 mM	0.1110 mL	0.5548 mL	1.1095 mL	2.7738 mL
	25 mM	0.0888 mL	0.4438 mL	0.8876 mL	2.2190 mL
	30 mM	0.0740 mL	0.3698 mL	0.7397 mL	1.8492 mL
	40 mM	0.0555 mL	0.2774 mL	0.5548 mL	1.3869 mL
	50 mM	0.0444 mL	0.2219 mL	0.4438 mL	1.1095 mL
	60 mM	0.0370 mL	0.1849 mL	0.3698 mL	0.9246 mL
Ethanol	80 mM	0.0277 mL	0.1387 mL	0.2774 mL	0.6934 mL
Ethanol	100 mM	0.0222 mL	0.1110 mL	0.2219 mL	0.5548 mL

INT-777 Related Classifications

Endocrinology

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

INT-7771199796-29-6S-EMCAINT777INT 777G protein-coupled Bile Acid Receptor 1G-protein coupled receptor 19GPCR19TGR5GPBAR1Inhibitorinhibitorinhibit

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INT-777 (Synonyms: S-EMCA)

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Other Forms of INT-777:

INT-777 Related Antibodies

35 Publications Citing Use of MCE INT-777

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Complete Stock Solution Preparation Table

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