| Size | Price | Stock | Qty |
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| 5mg | |||
| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: =99.98%
| Targets |
TGR5; FXR
Hyocholic Acid targets the G protein-coupled receptor TGR5 and the nuclear receptor FXR. It promotes GLP-1 secretion via activating TGR5 and inhibiting FXR in enteroendocrine cells. This dual mechanism drives its unique effects on GLP-1 secretion and glucose homeostasis. Activation of TGR5 by HCA stimulates incretin hormone secretion, while FXR inhibition further enhances this effect. |
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| ln Vitro |
In STC-1 and NCI-H716 cells, HCA (25 and 50 μM, 24 h) increases GLP-1 protein secretion[3]. In STC-1 and NCI-H716 cells, HCA (25 and 50 μM, 24 h) increases the transcription of the proglucagon gene[3].
In vitro, HCA (25 and 50 µM, 24 h) upregulates GLP-1 protein secretion in STC-1 and NCI-H716 enteroendocrine cells. It also upregulates proglucagon gene transcription in these cells. The compound's effects on GLP-1 secretion are mediated through TGR5 activation and FXR inhibition. HCA shows potent effects on incretin hormone secretion in cell-based assays. |
| ln Vivo |
Pigs' blood glucose rise brought on by BA depletion is suppressed by hyocholic acid (20 mg/kg, po)[3]. In diabetic mouse models, hydroxycholic acid (100 mg/kg/day, po) enhances serum fasting GLP-1 secretion and glucose homeostasis [3].
Hyocholic acid (HCA) and its derivatives are found in trace amounts in human blood but constitute approximately 76% of the bile acid (BA) pool in pigs, a species known for its exceptional resistance to type 2 diabetes. Here, we show that BA depletion in pigs suppressed secretion of glucagon-like peptide-1 (GLP-1) and increased blood glucose levels. HCA administration in diabetic mouse models improved serum fasting GLP-1 secretion and glucose homeostasis to a greater extent than tauroursodeoxycholic acid. HCA upregulated GLP-1 production and secretion in enteroendocrine cells via simultaneously activating G-protein-coupled BA receptor, TGR5, and inhibiting farnesoid X receptor (FXR), a unique mechanism that is not found in other BA species. We verified the findings in TGR5 knockout, intestinal FXR activation, and GLP-1 receptor inhibition mouse models. Finally, we confirmed in a clinical cohort, that lower serum concentrations of HCA species were associated with diabetes and closely related to glycemic markers.[3] In vivo, HCA (20 mg/kg, p.o.) suppresses bile acid depletion-induced blood glucose increase in pigs. HCA (100 mg/kg/day, p.o.) improves serum fasting GLP-1 secretion and glucose homeostasis in diabetic mouse models. The compound outperforms other compounds such as tauroursodeoxycholic acid (TUDCA) and even metformin in diabetic mouse models. |
| Enzyme Assay |
The in vitro assay for Hyocholic Acid involves measuring its effects on GLP-1 secretion in enteroendocrine cell lines (STC-1 and NCI-H716). Cells are treated with HCA at 25 and 50 µM for 24 hours. GLP-1 protein secretion is measured by ELISA. Proglucagon gene transcription is assessed by RT-qPCR. TGR5 activation and FXR inhibition are confirmed using specific pathway inhibitors or reporter assays.
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| Cell Assay |
Western Blot Analysis[3]
Cell Types: NCI-H716 cells Tested Concentrations: 50 μM Incubation Duration: 48 h Experimental Results: Inhibited the high expression of SHP (small heterodimer partner) induced by the FXR agonist. Cellular assays for Hyocholic Acid are performed using STC-1 and NCI-H716 enteroendocrine cells. Cells are treated with HCA at varying concentrations for 24 hours. GLP-1 secretion is measured in the culture medium by ELISA. Proglucagon mRNA levels are quantified by RT-qPCR. The involvement of TGR5 and FXR is confirmed using receptor-specific agonists or antagonists. |
| Animal Protocol |
Animal/Disease Models: BA depletion pigs[3]
Doses: 20 mg/kg Route of Administration: Oral administration (po) Experimental Results: Attenuated the increased blood glucose levels corresponding with GLP-1 decrease. Animal/Disease Models: db/db model, and the high-fat diet and streptozotocin (HFD+STZ) induced diabetic model[3] Doses: 100 mg/kg/day Route of Administration: Oral administration (po) Experimental Results: Improved oral glucose tolerances shown by lower glucose levels. Increased circulating active GLP- 1 levels and fasting insulin levels. In vivo animal studies are conducted in pigs and diabetic mouse models. HCA is administered orally. In pigs, HCA (20 mg/kg, p.o.) suppresses bile acid depletion-induced blood glucose increase. In diabetic mouse models, HCA (100 mg/kg/day, p.o.) improves serum fasting GLP-1 secretion and glucose homeostasis. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Known human metabolites include 24-O-glucuronidecholine and 6-O-glucuronidecholine. Pharmacokinetic data for Hyocholic Acid are not extensively detailed in the available sources. The compound is administered orally in animal studies. It is a naturally occurring bile acid with known enterohepatic circulation. Powder formulations should be stored at -20°C for up to 3 years or 4°C for up to 2 years; solutions should be stored at -80°C for up to 6 months or -20°C for up to 1 month. |
| Toxicity/Toxicokinetics |
Toxicity data for Hyocholic Acid are not reported in the available sources. As a naturally occurring bile acid found in pigs, it is generally considered to have a favorable safety profile. Specific toxicological studies have not been described. The compound is intended for research use only.
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| References |
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| Additional Infomation |
Hyocholic is a trihydroxy-5β-cholanic acid, with the three hydroxyl substituents located at the 3α, 6α, and 7α positions. It is found in mouse and human urine and in rats as a metabolite. It is a C24 steroid, 6α-hydroxy steroid, 7α-hydroxy steroid, belonging to the mouse cholic acid class of compounds. It is the conjugate acid of Hyocholic. Data on the reported presence of Hyocholic in Homo sapiens are available.
Hyocholic Acid is a research compound for studying metabolic disorders, particularly type 2 diabetes. It is a naturally occurring bile acid that promotes GLP-1 secretion. References describing its discovery and characterization include Zheng X, et al. Nat Commun. 2021 Mar 5;12(1):1487 and Zheng X, et al. Cell Metab. 2021 Apr 6;33(4):791-803.e7. The compound is available from commercial suppliers for research use only. |
| Molecular Formula |
C24H40O5
|
|---|---|
| Molecular Weight |
408.5714
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| Exact Mass |
408.287
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| CAS # |
547-75-1
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| Related CAS # |
Hyocholic Acid-d4;Hyocholic Acid-d5
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| PubChem CID |
92805
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| Appearance |
White to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
565.7±40.0 °C at 760 mmHg
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| Melting Point |
188-189ºC
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| Flash Point |
310.0±23.8 °C
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| Vapour Pressure |
0.0±3.5 mmHg at 25°C
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| Index of Refraction |
1.558
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| LogP |
3.82
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
637
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| Defined Atom Stereocenter Count |
11
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| SMILES |
C[C@H](CCC(=O)O)[C@H]1CC[C@H]2[C@H]3[C@H](CC[C@]12C)[C@@]4(C)CC[C@H](C[C@H]4[C@H]([C@H]3O)O)O
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| InChi Key |
DKPMWHFRUGMUKF-KWXDGCAGSA-N
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| InChi Code |
InChI=1S/C24H40O5/c1-13(4-7-19(26)27)15-5-6-16-20-17(9-11-23(15,16)2)24(3)10-8-14(25)12-18(24)21(28)22(20)29/h13-18,20-22,25,28-29H,4-12H2,1-3H3,(H,26,27)/t13-,14-,15-,16+,17+,18+,20+,21-,22+,23-,24-/m1/s1
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| Chemical Name |
(4R)-4-[(3R,5R,6R,7S,8S,9S,10R,13R,14S,17R)-3,6,7-trihydroxy-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
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| Synonyms |
gamma-Muricholic acid; Iocholic acid; 3alpha,6alpha,7alpha-Trihydroxy-5beta-cholan-24-oic acid; (4R)-4-[(3R,5R,6R,7S,8S,9S,10R,13R,14S,17R)-3,6,7-trihydroxy-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; 2H5H0Q47FL; CHEBI:81244;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~152.97 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.12 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4476 mL | 12.2378 mL | 24.4756 mL | |
| 5 mM | 0.4895 mL | 2.4476 mL | 4.8951 mL | |
| 10 mM | 0.2448 mL | 1.2238 mL | 2.4476 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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