Obeticholic Acid | INT747 | 6-ECDCA | CAS#459789-99-2 | FXR agonist

MedKoo Cat#: 522440 | Name: Obeticholic Acid

Description:

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

Obeticholic Acid (INT747; 6-ECDCA) is a novel derivative of cholic acid which acts as a potent and selective FXR agonist displaying anticholeretic activity in an in vivo rat model of cholestasis. It inhibits vascular smooth muscle cell inflammation and migration as well as promotes adipocyte differentiation and regulates adipose cell function in vivo.

Chemical Structure

Obeticholic Acid

CAS# 459789-99-2

Theoretical Analysis

MedKoo Cat#: 522440

Name: Obeticholic Acid

CAS#: 459789-99-2

Chemical Formula: C26H44O4

Exact Mass: 420.3240

Molecular Weight: 420.63

Elemental Analysis: C, 74.24; H, 10.54; O, 15.21

Price and Availability

Size	Price	Availability
50mg	USD 150.00	Ready to ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 950.00	Ready to ship
1g	USD 1,650.00	Ready to ship
2g	USD 2,950.00	Ready to ship
5g	USD 5,950.00	Ready to ship

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Related CAS #

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Synonym

6-Ethylchenodeoxycholic acid; Obeticholic acid; INT 747; INT-747; INT747; 6-ECDCA; Ocaliva.

IUPAC/Chemical Name

(4R)-4-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid

InChi Key

ZXERDUOLZKYMJM-ZWECCWDJSA-N

InChi Code

InChI=1S/C26H44O4/c1-5-17-21-14-16(27)10-12-26(21,4)20-11-13-25(3)18(15(2)6-9-22(28)29)7-8-19(25)23(20)24(17)30/h15-21,23-24,27,30H,5-14H2,1-4H3,(H,28,29)/t15-,16-,17-,18-,19+,20+,21+,23+,24-,25-,26-/m1/s1

SMILES Code

C[C@@H]([C@H]1CC[C@@]2([H])[C@]3([H])[C@H](O)[C@H](CC)[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)CCC(O)=O

Appearance

White to off-white 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, not in water

Shelf Life

>2 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

Certificate of Analysis

View CoA: current batch, Lot#X7P05R19

QC Data

View QC data: current batch, Lot#X7P05R19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Obeticholic acid (INT-747) is an active FXR agonist with an EC50 of 99 nM (FXR).

In vitro activity:

The aim of this study was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0–2.5 μM) of OCA were added to culture media and, after 3–10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin VFITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 μM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anticancerogenic effects against mucinous and mixed iCCA cells, in vitro. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXRmediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients. PLoS One. 2019; 14(1): e0210077. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345424/

In vivo activity:

This study assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after obeticholic acid (OCA) intervention for nine and 18 weeks. 32 mice were fed with HFHS diet (fat 60% kcal, carbohydrate 20% kcal, protein 20% kcal (Research Diets, New Brunswick, NJ, USA) and carbohydrates (18.9 g/L sucrose and 23.1 g/L fructose) in drinking water) for nine weeks to induce MDs and 12 mice were fed with normal chow. Then HFHS diet mice were divided into three groups (n = 10–12 per group): MO; mice were daily oral gavage with OCA (Selleck, USA) (2 mg/mL in carboxymethyl cellulose (CMC-Na), 5 mL/kg) ; (2) MA, mice were daily oral gavage with antibiotics cocktail containing1.86 mg ampicillin, 1.86 mg neomycin sulfate, 1.2 mg metronidazole and 0.96 mg vancomycin (Sigma-Aldrich, St. Louis, MO, USA) in 300 μL double distilled water ; M, mice were oral gavage with an equal volume of CMC-Na. Meanwhile, normal chow mice were oral gavage with an equal volume of CMC-Na as the control group (C).The GTT results showed that supplementation with OCA decreased the elevated fasting glucose in HFHS diet mice. These results supported that gut dysbiosis contributed to MDs in HFHS diet mice, which could be improved by OCA supplementation. Our findings highly suggested that the inhibiting effect of OCA on the anxietyrelated bacteria may be transmitted from the gut to the brain via the “gut microbiota–brain” axis. Thus, our findings of OCA in improving the ‘leaky gut’ and reducing the LPS-producing bacteria in HFHS-diet MDs mice could partially explain how orally OCA supplementation reduced neuroinflammation in the hippocampus via the ”gut–brain” axis. Nutrients. 2021 Mar; 13(3): 940. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999854/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	237.70

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 420.63 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. Di Matteo S, Nevi L, Costantini D, Overi D, Carpino G, Safarikia S, Giulitti F, Napoletano C, Manzi E, De Rose AM, Melandro F, Bragazzi M, Berloco PB, Giuliante F, Grazi G, Giorgi A, Cardinale V, Adorini L, Gaudio E, Alvaro D. The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma. PLoS One. 2019 Jan 24;14(1):e0210077. doi: 10.1371/journal.pone.0210077. PMID: 30677052; PMCID: PMC6345424. 2. Anfuso B, Tiribelli C, Adorini L, Rosso N. Obeticholic acid and INT-767 modulate collagen deposition in a NASH in vitro model. Sci Rep. 2020 Feb 3;10(1):1699. doi: 10.1038/s41598-020-58562-x. PMID: 32015483; PMCID: PMC6997404. 3. .Wu L, Han Y, Zheng Z, Zhu S, Chen J, Yao Y, Yue S, Teufel A, Weng H, Li L, Wang B. Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice. Nutrients. 2021 Mar 15;13(3):940. doi: 10.3390/nu13030940. PMID: 33803974; PMCID: PMC7999854. 4. de Haan LR, Verheij J, van Golen RF, Horneffer-van der Sluis V, Lewis MR, Beuers UHW, van Gulik TM, Olde Damink SWM, Schaap FG, Heger M, Olthof PB. Unaltered Liver Regeneration in Post-Cholestatic Rats Treated with the FXR Agonist Obeticholic Acid. Biomolecules. 2021 Feb 10;11(2):260. doi: 10.3390/biom11020260. PMID: 33578971; PMCID: PMC7916678.

In vitro protocol:

In vivo protocol:

1..Wu L, Han Y, Zheng Z, Zhu S, Chen J, Yao Y, Yue S, Teufel A, Weng H, Li L, Wang B. Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice. Nutrients. 2021 Mar 15;13(3):940. doi: 10.3390/nu13030940. PMID: 33803974; PMCID: PMC7999854. 2. de Haan LR, Verheij J, van Golen RF, Horneffer-van der Sluis V, Lewis MR, Beuers UHW, van Gulik TM, Olde Damink SWM, Schaap FG, Heger M, Olthof PB. Unaltered Liver Regeneration in Post-Cholestatic Rats Treated with the FXR Agonist Obeticholic Acid. Biomolecules. 2021 Feb 10;11(2):260. doi: 10.3390/biom11020260. PMID: 33578971; PMCID: PMC7916678.

1: Yao Q, Wang B, Yu J, Pan Q, Yu Y, Feng X, Chen W, Yang J, Gao C, Cao H. ROS- responsive and biomimetic nanoparticle delivery of obeticholic acid mitigates primary sclerosing cholangitis via mitochondria- induced apoptosis. J Control Release. 2024 Aug 6:S0168-3659(24)00545-5. doi: 10.1016/j.jconrel.2024.08.006. Epub ahead of print. PMID: 39117112. 2: Jing D, Liu J, Qin D, Lin J, Li T, Li Y, Duan M. Obeticholic acid ameliorates sepsis-induced renal mitochondrial damage by inhibiting the NF-κb signaling pathway. Ren Fail. 2024 Dec;46(2):2368090. doi: 10.1080/0886022X.2024.2368090. Epub 2024 Aug 6. PMID: 39108162; PMCID: PMC11308967. 3: Sylvia D, Tomas K, Marian M, Martin J, Dagmar S, Peter J. The treatment of primary biliary cholangitis: from shadow to light. Therap Adv Gastroenterol. 2024 Jul 29;17:17562848241265782. doi: 10.1177/17562848241265782. PMID: 39081664; PMCID: PMC11287753. 4: Hu X, Ge J, Wen Y. Computational study of novel natural agonists targeting farnesoid X receptor. Sci Rep. 2024 Jul 30;14(1):17597. doi: 10.1038/s41598-024-68526-0. PMID: 39079973; PMCID: PMC11289082. 5: Chen L, Wang B, Li H, Mao J, Liang Z, Chen Y, Yu M, Liu Y, Liao Z, Yang Y, Wu X, Wang H, Yang Y, Xiang R, Zhang L, Li Z. Design, synthesis, and biological evaluation of novel highly selective non-carboxylic acid FABP1 inhibitors. Eur J Med Chem. 2024 Jul 22;276:116705. doi: 10.1016/j.ejmech.2024.116705. Epub ahead of print. PMID: 39067439. 6: Bilson J, Scorletti E, Swann JR, Byrne CD. Bile Acids as Emerging Players at the Intersection of Steatotic Liver Disease and Cardiovascular Diseases. Biomolecules. 2024 Jul 12;14(7):841. doi: 10.3390/biom14070841. PMID: 39062555; PMCID: PMC11275019. 7: Kim C, Tsai TH, Lopez R, McCullough A, Kasumov T. Obeticholic acid's effect on HDL function in MASH varies by diabetic status. Lipids. 2024 Jul 16. doi: 10.1002/lipd.12408. Epub ahead of print. PMID: 39014264. 8: Yan M, Man S, Ma L, Guo L, Huang L, Gao W. Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives. Clin Mol Hepatol. 2024 Jul 11. doi: 10.3350/cmh.2024.0315. Epub ahead of print. PMID: 38988278. 9: Luo X, Lu LG. Progress in the Management of Patients with Cholestatic Liver Disease: Where Are We and Where Are We Going? J Clin Transl Hepatol. 2024 Jun 28;12(6):581-588. doi: 10.14218/JCTH.2023.00519. Epub 2024 May 11. PMID: 38974958; PMCID: PMC11224908. 10: Maceo Heilman B, Mote K, Batchelor W, Rowaan C, Gonzalez A, Arrieta E, Ruggeri M, Ziebarth N, Cabrera-Ghayouri S, Dibas M, Parel JM, Manns F. Effect of compound treatments on mouse lens viscoelasticity. Exp Eye Res. 2024 Jul 6;246:109992. doi: 10.1016/j.exer.2024.109992. Epub ahead of print. PMID: 38972445. 11: Sun L, Yang N, Liu Z, Ye X, Cheng M, Deng L, Zhang J, Wu J, Shi M, Liao W. Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis. J Biomed Sci. 2024 Jun 29;31(1):66. doi: 10.1186/s12929-024-01052-3. PMID: 38951890; PMCID: PMC11218316. 12: Baumeister T, Proaño-Vasco A, Metwaly A, Kleigrewe K, Kuznetsov A, Schömig L, Borgmann M, Khiat M, Anand A, Böttcher K, Haller D, Dunkel A, Somoza V, Reiter S, Meng C, Thimme R, Schmid RM, Patil DT, Burgermeister E, Huang Y, Sun Y, Wang HH, Wang TC, Abrams JA, Quante M. Microbiota metabolized Bile Acids accelerate Gastroesophageal Adenocarcinoma via FXR inhibition. bioRxiv [Preprint]. 2024 Jun 12:2024.06.11.598405. doi: 10.1101/2024.06.11.598405. PMID: 38915718; PMCID: PMC11195123. 13: Fu J, Zhang P, Sun Z, Lu G, Cao Q, Chen Y, Wu W, Zhang J, Zhuang C, Sheng C, Xu J, Lu Y, Wang P. A combined nanotherapeutic approach targeting farnesoid X receptor, ferroptosis, and fibrosis for nonalcoholic steatohepatitis treatment. Acta Pharm Sin B. 2024 May;14(5):2228-2246. doi: 10.1016/j.apsb.2024.02.017. Epub 2024 Feb 26. PMID: 38799646; PMCID: PMC11121165. 14: De Vincentis A, Ampuero J, Terracciani F, D'Amato D, Gerussi A, Cristoferi L, Cazzagon N, Bonaiuto E, Floreani A, Calvaruso V, Cadamuro L, Degasperi E, Morgando A, Vanni E, Lleo A, Colapietro F, Alvaro D, Castellaneta A, Labanca S, Viganò M, Distefano M, Pace Palitti V, Ricci C, De Matthaeis N, Marzioni M, Gómez-Dominguez E, Montero JL, Molina E, Garcia-Buey L, Casado M, Berenguer M, Conde I, Simon MA, Fuentes J, Costa-Moreira P, Macedo G, Jorquera F, Morillas RM, Presa J, Sousa JM, Gomes D, Santos L, Olveira A, Hernandez-Guerra M, Aburruza L, Santos A, Carvalho A, Uriz J, Gutierrez ML, Perez E, Chessa L, Pellicelli A, Marignani M, Muratori L, Niro GA, Brunetto M, Ponziani FR, Pompili M, Marra F, Galli A, Mussetto A, Alagna G, Simone L, Bertino G, Rosina F, Cozzolongo R, Russello M, Baiocchi L, Saitta C, Terreni N, Zolfino T, Rigamonti C, Vigano R, Cuccorese G, Pozzoni P, Pedone C, Grasso S, Picardi A, Invernizzi P, Sacco R, Izzi A, Fernandez-Rodriguez C, Vespasiani-Gentilucci U, Carbone M. Development and Validation of a Scoring System to Predict Response to Obeticholic Acid in Primary Biliary Cholangitis. Clin Gastroenterol Hepatol. 2024 May 22:S1542-3565(24)00482-8. doi: 10.1016/j.cgh.2024.05.008. Epub ahead of print. PMID: 38782175. 15: Miao H, Tang X, Cui Y, Shi J, Xiong X, Wang C, Zhang Y. Obeticholic Acid Inhibit Mitochondria Dysfunction Via Regulating ERK1/2-DRP Pathway to Exert Protective Effect on Lipopolysaccharide-Induced Myocardial Injury. Adv Biol (Weinh). 2024 Jul;8(7):e2300576. doi: 10.1002/adbi.202300576. Epub 2024 May 10. PMID: 38728002. 16: Hou L, Wang H, Yan M, Cai Y, Zheng R, Ma Y, Tang W, Jiang W. Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome. Biochim Biophys Acta Mol Basis Dis. 2024 Jun;1870(5):167221. doi: 10.1016/j.bbadis.2024.167221. Epub 2024 May 6. PMID: 38718845. 17: Narayanan AK, Surendran S, Balakrishnan D, Gopalakrishnan U, Malick S, Valsan A, Philips CA, Watson CJE. A Short Review on Obeticholic Acid: An Effective Modulator of Farnesoid X Receptor. Curr Rev Clin Exp Pharmacol. 2024;19(3):225-233. doi: 10.2174/0127724328239536230919070001. PMID: 38708917. 18: Xiong A, Lu L, Jiang K, Wang X, Chen Y, Wang X, Zhang W, Zhuge Y, Huang W, Li L, Liao Q, Yang F, Liu P, Ding L, Wang Z, Yang L. Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Arch Toxicol. 2024 Aug;98(8):2557-2576. doi: 10.1007/s00204-024-03762-x. Epub 2024 May 4. PMID: 38703205. 19: Gómez E, Montero JL, Molina E, García-Buey L, Casado M, Fuentes J, Simón MA, Díaz-González A, Jorquera F, Morillas RM, Presa J, Berenguer M, Conde MI, Olveira A, Macedo G, Garrido I, Hernández-Guerra M, Olivas I, Rodríguez-Tajes S, Londoño M, Sousa JM, Ampuero J, Romero-González E, González-Padilla S, Escudero- García D, Carvalho A, Santos A, Gutiérrez ML, Pérez-Fernández E, Aburruza L, Uriz J, Gomes D, Santos L, Martínez-González J, Albillos A, Fernández-Rodríguez CM. Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real- world practice. Aliment Pharmacol Ther. 2024 Jun;59(12):1604-1615. doi: 10.1111/apt.18004. Epub 2024 May 1. PMID: 38690746. 20: Akepati PR, Gochanour EM. Investigational farnesoid X receptor agonists for the treatment of primary biliary cholangitis. Expert Opin Investig Drugs. 2024 Jun;33(6):627-638. doi: 10.1080/13543784.2024.2348743. Epub 2024 May 7. PMID: 38676426.