Obeticholic Acid
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MedKoo CAT#: 522440

CAS#: 459789-99-2

Description: 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

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Obeticholic Acid
CAS# 459789-99-2
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522440
Name: Obeticholic Acid
CAS#: 459789-99-2
Chemical Formula: C26H44O4
Exact Mass: 420.32
Molecular Weight: 420.630
Elemental Analysis: C, 74.24; H, 10.54; O, 15.21

Price and Availability

Size Price Availability Quantity
50mg USD 150 Ready to ship
100mg USD 250 Ready to ship
200mg USD 450 Ready to ship
500mg USD 950 Ready to ship
1g USD 1650 Ready to ship
2g USD 2950 Ready to ship
5g USD 5950 Ready to ship
Bulk inquiry

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:

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 237.70

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.

Recalculate based on batch purity %
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: 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.
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.

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1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548806/ PubMed PMID: 31644113.

2: Fiorucci S, Di Giorgio C, Distrutti E. Obeticholic Acid: An Update of Its Pharmacological Activities in Liver Disorders. Handb Exp Pharmacol. 2019;256:283-295. doi: 10.1007/164_2019_227. Review. PubMed PMID: 31201552.

3: Patient Group Input Submissions: Obeticholic Acid (Ocaliva): (Intercept Pharma Canada, Inc.): Indication: For the treatment of primary biliary cholangitis [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Aug. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK534960/ PubMed PMID: 30525352.

4: Pharmacoeconomic Review Report: Obeticholic Acid (Ocaliva): (Intercept Pharma Canada, Inc.): Indication: For the treatment of primary biliary cholangitis [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK534952/ PubMed PMID: 30525351.

5: CADTH Canadian Drug Expert Committee Recommendation: Obeticholic Acid (Ocaliva — Intercept Pharmaceuticals Canada): Indication: Primary biliary cholangitis [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Jul. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK534959/ PubMed PMID: 30525350.

6: Clinical Review Report: Obeticholic Acid (Ocaliva): (Intercept Pharmaceuticals Canada, Inc.): Indication: For the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK534942/ PubMed PMID: 30525349.

7: Abenavoli L, Falalyeyeva T, Boccuto L, Tsyryuk O, Kobyliak N. Obeticholic Acid: A New Era in the Treatment of Nonalcoholic Fatty Liver Disease. Pharmaceuticals (Basel). 2018 Oct 11;11(4). pii: E104. doi: 10.3390/ph11040104. Review. PubMed PMID: 30314377; PubMed Central PMCID: PMC6315965.

8: Hvas CL, Ott P, Paine P, Lal S, Jørgensen SP, Dahlerup JF. Obeticholic acid for severe bile acid diarrhea with intestinal failure: A case report and review of the literature. World J Gastroenterol. 2018 Jun 7;24(21):2320-2326. doi: 10.3748/wjg.v24.i21.2320. Review. PubMed PMID: 29881241; PubMed Central PMCID: PMC5989246.

9: Gitto S, Guarneri V, Sartini A, Andreone P. The use of obeticholic acid for the management of non-viral liver disease: current clinical practice and future perspectives. Expert Rev Gastroenterol Hepatol. 2018 Feb;12(2):165-171. doi: 10.1080/17474124.2018.1399060. Epub 2017 Nov 3. Review. PubMed PMID: 29082798.

10: Jhaveri MA, Kowdley KV. New developments in the treatment of primary biliary cholangitis - role of obeticholic acid. Ther Clin Risk Manag. 2017 Aug 21;13:1053-1060. doi: 10.2147/TCRM.S113052. eCollection 2017. Review. PubMed PMID: 28860789; PubMed Central PMCID: PMC5572954.

11: Bowlus CL. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection. Hepat Med. 2016 Sep 1;8:89-95. doi: 10.2147/HMER.S91709. eCollection 2016. Review. PubMed PMID: 27621676; PubMed Central PMCID: PMC5012622.

12: Ali AH, Lindor KD. Obeticholic acid for the treatment of primary biliary cholangitis. Expert Opin Pharmacother. 2016 Sep;17(13):1809-15. doi: 10.1080/14656566.2016.1218471. Epub 2016 Aug 9. Review. PubMed PMID: 27468093.

13: Markham A, Keam SJ. Obeticholic Acid: First Global Approval. Drugs. 2016 Aug;76(12):1221-6. doi: 10.1007/s40265-016-0616-x. Review. PubMed PMID: 27406083.

14: Trivedi PJ, Hirschfield GM, Gershwin ME. Obeticholic acid for the treatment of primary biliary cirrhosis. Expert Rev Clin Pharmacol. 2016;9(1):13-26. doi: 10.1586/17512433.2015.1092381. Epub 2015 Nov 7. Review. PubMed PMID: 26549695.

15: Arrese M, Cabrera D, Barrera F. Obeticholic acid: expanding the therapeutic landscape of NASH. Ann Hepatol. 2015 May-Jun;14(3):430-2. Review. PubMed PMID: 25864227.

16: Silveira MG, Lindor KD. Obeticholic acid and budesonide for the treatment of primary biliary cirrhosis. Expert Opin Pharmacother. 2014 Feb;15(3):365-72. doi: 10.1517/14656566.2014.873404. Epub 2014 Jan 2. Review. PubMed PMID: 24382005.