INT-777 | CAS#1199796-29-6 | TGR5 agonist

MedKoo Cat#: 555594 | Name: INT-777

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

INT-777 is a semisynthetic bile acid that acts as an agonist of TGR5 (EC50 = 0.82 µM). INT-777 mitigates inflammatory response in human endometriotic stromal cells: A therapeutic implication for endometriosis.

Chemical Structure

INT-777

CAS#1199796-29-6

Theoretical Analysis

MedKoo Cat#: 555594

Name: INT-777

CAS#: 1199796-29-6

Chemical Formula: C27H46O5

Exact Mass: 450.3345

Molecular Weight: 450.66

Elemental Analysis: C, 71.96; H, 10.29; O, 17.75

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 650.00	2 Weeks

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Related CAS #

No Data

Synonym

INT-777; INT 777; INT777; 6-EMCA; S-EMCA; HY-15677;

IUPAC/Chemical Name

(2S,4R)-4-((3R,5S,6R,7R,8R,9S,10S,12S,13R,14S,17R)-6-ethyl-3,7,12-trihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methylpentanoic acid

InChi Key

NPBCMXATLRCCLF-IRRLEISYSA-N

InChi Code

InChi Code InChI=1S/C27H46O5/c1-6-17-20-12-16(28)9-10-26(20,4)21-13-22(29)27(5)18(14(2)11-15(3)25(31)32)7-8-19(27)23(21)24(17)30/h14-24,28-30H,6-13H2,1-5H3,(H,31,32)/t14-,15+,16-,17-,18-,19+,20+,21+,22+,23+,24-,26+,27-/m1/s1

SMILES Code

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@]4([H])[C@H](C)C[C@H](C)C(O)=O)([H])C1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

INT-777 (S-EMCA) is a potent TGR5 agonist with an EC50 of 0.82 μM.

In vitro activity:

Addition of INT-777, and less potently UDCA, decreased colonic secretion in seromuscular stripped dC by -58.17± 2.6%. INT-777 effect on basal secretion was reduced in neuron-free and TTX-treated mucosal-submucosal preparations. Reference: Neurogastroenterol Motil. 2016 Nov;28(11):1663-1676. https://pubmed.ncbi.nlm.nih.gov/27259385/

In vivo activity:

The medium (30μg/kg) and high (90μg/kg) doses of INT-777 administration significantly improved the neurological deficits on modified Garcia test and beam balance test at 24 h after SAH compared with the vehicle group (Fig. 2C–D). Consistently, the brain water contents in the ipsilateral (left) and contralateral (right) hemisphere were significantly increased in the SAH groups compared to the sham group (Fig. 2E), which was significantly decreased by the medium and high doses of INT-777 treatment (Fig. 2E). Reference: Brain Behav Immun. 2021 Jan;91:587-600. https://pubmed.ncbi.nlm.nih.gov/32961266/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	66.57
	DMF:PBS (pH 7.2) (1:1)	0.5	1.11
	DMSO	25.5	56.58
	Ethanol	37.5	83.21

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 450.66 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Duboc H, Tolstanova G, Yuan PQ, Wu V, Kaji I, Biraud M, Akiba Y, Kaunitz J, Million M, Tache Y, Larauche M. 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 Nov;28(11):1663-1676. doi: 10.1111/nmo.12866. Epub 2016 Jun 3. PMID: 27259385; PMCID: PMC5083223. 2. Hu X, Yan J, Huang L, Araujo C, Peng J, Gao L, Liu S, Tang J, Zuo G, Zhang JH. INT-777 attenuates NLRP3-ASC inflammasome-mediated neuroinflammation via TGR5/cAMP/PKA signaling pathway after subarachnoid hemorrhage in rats. Brain Behav Immun. 2021 Jan;91:587-600. doi: 10.1016/j.bbi.2020.09.016. Epub 2020 Sep 19. PMID: 32961266; PMCID: PMC7749833. 3. Zuo G, Zhang T, Huang L, Araujo C, Peng J, Travis Z, Okada T, Ocak U, Zhang G, Tang J, Lu X, Zhang JH. Activation of TGR5 with INT-777 attenuates oxidative stress and neuronal apoptosis via cAMP/PKCε/ALDH2 pathway after subarachnoid hemorrhage in rats. Free Radic Biol Med. 2019 Nov 1;143:441-453. doi: 10.1016/j.freeradbiomed.2019.09.002. Epub 2019 Sep 4. PMID: 31493504; PMCID: PMC6848789.

In vitro protocol:

In vivo protocol:

1. Hu X, Yan J, Huang L, Araujo C, Peng J, Gao L, Liu S, Tang J, Zuo G, Zhang JH. INT-777 attenuates NLRP3-ASC inflammasome-mediated neuroinflammation via TGR5/cAMP/PKA signaling pathway after subarachnoid hemorrhage in rats. Brain Behav Immun. 2021 Jan;91:587-600. doi: 10.1016/j.bbi.2020.09.016. Epub 2020 Sep 19. PMID: 32961266; PMCID: PMC7749833. 2. Zuo G, Zhang T, Huang L, Araujo C, Peng J, Travis Z, Okada T, Ocak U, Zhang G, Tang J, Lu X, Zhang JH. Activation of TGR5 with INT-777 attenuates oxidative stress and neuronal apoptosis via cAMP/PKCε/ALDH2 pathway after subarachnoid hemorrhage in rats. Free Radic Biol Med. 2019 Nov 1;143:441-453. doi: 10.1016/j.freeradbiomed.2019.09.002. Epub 2019 Sep 4. PMID: 31493504; PMCID: PMC6848789.

1: Lazarević S, Đanić M, Goločorbin-Kon S, Al-Salami H, Mikov M. Semisynthetic bile acids: a new therapeutic option for metabolic syndrome. Pharmacol Res. 2019 Aug;146:104333. doi: 10.1016/j.phrs.2019.104333. Epub 2019 Jun 26. Review. PubMed PMID: 31254667. 2: Zhuo W, Li B, Zhang D. Activation of G-protein-coupled bile acid receptor Gpbar1 (TGR5) inhibits degradation of type II collagen and aggrecan in human chondrocytes. Eur J Pharmacol. 2019 Aug 5;856:172387. doi: 10.1016/j.ejphar.2019.05.016. Epub 2019 May 7. PubMed PMID: 31075239. 3: Chen Y, Le TH, Du Q, Zhao Z, Liu Y, Zou J, Hua W, Liu C, Zhu Y. Genistein protects against DSS-induced colitis by inhibiting NLRP3 inflammasome via TGR5-cAMP signaling. Int Immunopharmacol. 2019 Jun;71:144-154. doi: 10.1016/j.intimp.2019.01.021. Epub 2019 Mar 19. PubMed PMID: 30901677. 4: Lyu D, Tang N, Wang J, Zhang Y, Chang J, Liu Z, Liu H. TGR5 agonist INT-777 mitigates inflammatory response in human endometriotic stromal cells: A therapeutic implication for endometriosis. Int Immunopharmacol. 2019 Jun;71:93-99. doi: 10.1016/j.intimp.2019.02.044. Epub 2019 Mar 14. PubMed PMID: 30878820. 5: Yang J, Hu J, Feng L, Yi S, Ye Z, Lin M, Liu X, Pu Y, Kijlstra A, Yang P, Li H. Decreased Expression of TGR5 in Vogt-Koyanagi-Harada (VKH) Disease. Ocul Immunol Inflamm. 2019 Feb 22:1-9. doi: 10.1080/09273948.2018.1560477. [Epub ahead of print] PubMed PMID: 30794473. 6: Robering JW, Gebhardt L, Wolf K, Kühn H, Kremer AE, Fischer MJM. Lysophosphatidic acid activates satellite glia cells and Schwann cells. Glia. 2019 May;67(5):999-1012. doi: 10.1002/glia.23585. Epub 2019 Jan 13. PubMed PMID: 30637823. 7: Iracheta-Vellve A, Calenda CD, Petrasek J, Ambade A, Kodys K, Adorini L, Szabo G. FXR and TGR5 Agonists Ameliorate Liver Injury, Steatosis, and Inflammation After Binge or Prolonged Alcohol Feeding in Mice. Hepatol Commun. 2018 Oct 15;2(11):1379-1391. doi: 10.1002/hep4.1256. eCollection 2018 Nov. PubMed PMID: 30411084; PubMed Central PMCID: PMC6211332. 8: Xiong Q, Huang H, Wang N, Chen R, Chen N, Han H, Wang Q, Siwko S, Liu M, Qian M, Du B. Metabolite-Sensing G Protein Coupled Receptor TGR5 Protects Host From Viral Infection Through Amplifying Type I Interferon Responses. Front Immunol. 2018 Oct 2;9:2289. doi: 10.3389/fimmu.2018.02289. eCollection 2018. PubMed PMID: 30333836; PubMed Central PMCID: PMC6176213. 9: Li S, Qiu M, Kong Y, Zhao X, Choi HJ, Reich M, Bunkelman BH, Liu Q, Hu S, Han M, Xie H, Rosenberg AZ, Keitel V, Kwon TH, Levi M, Li C, Wang W. Bile Acid G Protein-Coupled Membrane Receptor TGR5 Modulates Aquaporin 2-Mediated Water Homeostasis. J Am Soc Nephrol. 2018 Nov;29(11):2658-2670. doi: 10.1681/ASN.2018030271. Epub 2018 Oct 10. PubMed PMID: 30305310; PubMed Central PMCID: PMC6218869. 10: Webb GJ, Hirschfield GM. Work in Progress: Drugs in Development. Clin Liver Dis. 2018 Aug;22(3):501-515. doi: 10.1016/j.cld.2018.03.004. Epub 2018 May 17. Review. PubMed PMID: 30259849. 11: Wu X, Lv YG, Du YF, Hu M, Reed MN, Long Y, Suppiramaniam V, Hong H, Tang SS. Inhibitory effect of INT-777 on lipopolysaccharide-induced cognitive impairment, neuroinflammation, apoptosis, and synaptic dysfunction in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jan 10;88:360-374. doi: 10.1016/j.pnpbp.2018.08.016. Epub 2018 Aug 23. PubMed PMID: 30144494. 12: Huang H, Lei H, Yang F, Fan X, Dang Q, Li Y. Activation of the bile acid receptor GPBAR1 (TGR5) ameliorates interleukin-1β (IL-1β)- induced chondrocytes senescence. Biomed Pharmacother. 2018 Oct;106:1713-1719. doi: 10.1016/j.biopha.2018.06.154. Epub 2018 Jul 30. PubMed PMID: 30119246. 13: Eblimit Z, Thevananther S, Karpen SJ, Taegtmeyer H, Moore DD, Adorini L, Penny DJ, Desai MS. TGR5 activation induces cytoprotective changes in the heart and improves myocardial adaptability to physiologic, inotropic, and pressure-induced stress in mice. Cardiovasc Ther. 2018 Oct;36(5):e12462. doi: 10.1111/1755-5922.12462. Epub 2018 Aug 22. PubMed PMID: 30070769. 14: Wu X, Lv YG, Du YF, Chen F, Reed MN, Hu M, Suppiramaniam V, Tang SS, Hong H. Neuroprotective effects of INT-777 against Aβ(1-42)-induced cognitive impairment, neuroinflammation, apoptosis, and synaptic dysfunction in mice. Brain Behav Immun. 2018 Oct;73:533-545. doi: 10.1016/j.bbi.2018.06.018. Epub 2018 Jun 20. PubMed PMID: 29935310. 15: Li B, Yang N, Li C, Li C, Gao K, Xie X, Dong X, Yang J, Yang Q, Tong Z, Lu G, Li W. 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. doi: 10.1016/j.bbrc.2018.05.120. Epub 2018 Jun 7. PubMed PMID: 29859191. 16: Wang XX, Wang D, Luo Y, Myakala K, Dobrinskikh E, Rosenberg AZ, Levi J, Kopp JB, Field A, Hill A, Lucia S, Qiu L, Jiang T, Peng Y, Orlicky D, Garcia G, Herman-Edelstein M, D'Agati V, Henriksen K, Adorini L, Pruzanski M, Xie C, Krausz KW, Gonzalez FJ, Ranjit S, Dvornikov A, Gratton E, Levi M. FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity. J Am Soc Nephrol. 2018 Jan;29(1):118-137. doi: 10.1681/ASN.2017020222. Epub 2017 Oct 31. PubMed PMID: 29089371; PubMed Central PMCID: PMC5748904. 17: Comeglio P, Morelli A, Adorini L, Maggi M, Vignozzi L. Beneficial effects of bile acid receptor agonists in pulmonary disease models. Expert Opin Investig Drugs. 2017 Nov;26(11):1215-1228. doi: 10.1080/13543784.2017.1385760. Epub 2017 Oct 3. Review. PubMed PMID: 28949776. 18: Erice O, Labiano I, Arbelaiz A, Santos-Laso A, Munoz-Garrido P, Jimenez-Agüero R, Olaizola P, Caro-Maldonado A, Martín-Martín N, Carracedo A, Lozano E, Marin JJ, O'Rourke CJ, Andersen JB, Llop J, Gómez-Vallejo V, Padro D, Martin A, Marzioni M, Adorini L, Trauner M, Bujanda L, Perugorria MJ, Banales JM. Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression. Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt B):1335-1344. doi: 10.1016/j.bbadis.2017.08.016. Epub 2017 Sep 13. PubMed PMID: 28916388. 19: Lajczak NK, Saint-Criq V, O'Dwyer AM, Perino A, Adorini L, Schoonjans K, Keely SJ. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells. FASEB J. 2017 Sep;31(9):3848-3857. doi: 10.1096/fj.201601365R. Epub 2017 May 9. PubMed PMID: 28487283. 20: Pathak P, Liu H, Boehme S, Xie C, Krausz KW, Gonzalez F, Chiang JYL. Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism. J Biol Chem. 2017 Jun 30;292(26):11055-11069. doi: 10.1074/jbc.M117.784322. Epub 2017 May 6. PubMed PMID: 28478385; PubMed Central PMCID: PMC5491788.