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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Lithocholic acid analog; The primary targets of Allolithocholic acid include GPBAR1 (G protein-coupled bile acid receptor 1) and RORγt (retinoic acid receptor-related orphan receptor gamma t), positioning it as a dual modulator. Studies have shown that Allo-LCA (i.e., Allolithocholic acid) acts as a GPBAR1 agonist and an RORγt inverse agonist. Through GPBAR1, this compound regulates bile acid signaling pathways; through RORγt, it influences the differentiation of T helper 17 (Th17) cells. Additionally, this compound binds to ileal fatty acid-binding protein 6 (FABP6, also known as ILBP), which is involved in the intracellular transport of bile acids. At the cellular level, it inhibits macrophage M1 polarization and Th17 polarization of CD4+ T cells.
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| ln Vitro |
In cell-free systems, Allolithocholic acid exhibits activity as a GPBAR1 agonist and an RORγt inverse agonist. In vitro studies demonstrate that this compound prevents macrophage M1 polarization and Th17 polarization of CD4+ T cells, which is significant for modulating inflammatory responses. In immune cell studies, Allolithocholic acid (20 μM) increases the association of the nuclear hormone receptor Nur77 (Nr4a1) with the Foxp3 gene in isolated mouse CD4+ T cells, inducing their differentiation into regulatory T cells (Tregs). At the same concentration of 20 μM, it also induces the production of mitochondrial reactive oxygen species (ROS) in isolated mouse CD4+ T cells. These in vitro data indicate that this compound plays an important role in immunomodulation.
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| ln Vivo |
The in vivo activity of Allolithocholic acid is primarily studied using animal disease models. In a MASH (metabolic dysfunction-associated steatohepatitis) mouse model, administration of Allo-LCA (10 mg/kg/day) significantly ameliorated the disease phenotype. Studies demonstrate that this compound reverses high-fat/high-fructose diet combined with carbon tetrachloride-induced insulin resistance, pro-atherogenic lipid profile, liver steatosis, and fibrosis. Liver transcriptomic analysis revealed that Allo-LCA reversed the dysregulation of multiple pathways associated with immunological, inflammatory, and metabolic signaling. Furthermore, this compound restored bile acid homeostasis, reversed diet/CCl₄-induced shifts in bile acid pool composition, and restored adipose tissue histopathology and function by reducing the expression of leptin and resistin (two pro-inflammatory adipokines). It also improved the healthy composition of the intestinal microbiota.
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| Enzyme Assay |
The binding of Allolithocholic acid to receptors can be assessed using various in vitro methods. GPBAR1 agonist activity is typically evaluated using cell-based functional assays, such as quantifying downstream cAMP accumulation following receptor activation. For RORγt inverse agonist activity, fluorescence resonance energy transfer (FRET) or time-resolved fluorescence resonance energy transfer (TR-FRET) competition binding assays can be used to determine the binding affinity of the compound to the RORγt ligand-binding domain. In T cell differentiation studies, CD4+ T cells are isolated from mouse spleens and cultured under Treg-polarizing conditions (TGF-β and IL-2) in the presence or absence of Allolithocholic acid (20 μM). Treg differentiation is assessed by detecting Foxp3 expression via flow cytometry, and cellular metabolic changes are evaluated by measuring mitochondrial ROS production.
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| Cell Assay |
Cellular assays for Allolithocholic acid typically employ primary immune cell models. A typical protocol: CD4+ T cells are isolated from C57BL/6 mouse spleens using magnetic bead-based negative selection. Cells are seeded in plates coated with anti-CD3/CD28 antibodies and cultured in Treg-polarizing medium containing IL-2 and TGF-β. The experimental group receives 20 μM Allolithocholic acid, while the control group receives an equal volume of vehicle (e.g., DMSO, final concentration <0.1%). After 72-96 hours of culture, cells are harvested for flow cytometry analysis, and the proportion of Treg cells is detected using a Foxp3 staining kit. For macrophage polarization studies, bone marrow-derived macrophages can be incubated with Allolithocholic acid, and the expression changes of M1 markers (e.g., iNOS, IL-6) and M2 markers (e.g., Arg-1, IL-10) are detected by qPCR.
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| Animal Protocol |
In vivo studies of Allolithocholic acid primarily employ MASH/liver fibrosis mouse models. A typical protocol: Male C57BL/6J mice (6-8 weeks old) are fed a high-fat/high-fructose diet combined with intraperitoneal injection of carbon tetrachloride (CCl₄, twice weekly, 0.4 μL/g body weight) to induce the MASH model. After model establishment, the treatment group receives Allolithocholic acid (10 mg/kg/day, dissolved in corn oil or appropriate vehicle) by oral gavage daily, while the control group receives an equal volume of vehicle. After several weeks of treatment, animals are euthanized. Serum is collected to assess insulin resistance indicators and lipid profiles; liver tissues are collected for Oil Red O staining to evaluate steatosis and Sirius Red staining to assess fibrosis. Additionally, RNA sequencing is performed to analyze liver transcriptomic changes, bile acid profiles are measured, and cecal contents are collected for 16S rRNA sequencing to analyze gut microbiota composition.
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| ADME/Pharmacokinetics |
As a member of the bile acid family, Allolithocholic acid follows the enterohepatic circulation pattern of bile acids. This compound exists as an anion at physiological pH and therefore requires specific carrier proteins (e.g., ileal bile acid-binding protein) to facilitate transmembrane transport. In vivo, it is reabsorbed into the liver via the portal vein, subsequently secreted into bile, and then enters the intestine, forming an enterohepatic circuit. In rats, administration of Allolithocholic acid (6 mg/kg) reduces hepatic bile flow and the secretion of bile salts, cholesterol, and phospholipids. Predicted physicochemical properties: LogP approximately 4.38-5.02, pKa (strongest acidic) of 4.79, and low water solubility (approximately 5.05 × 10⁻⁴ g/L). Fecal levels of this compound are reduced in patients with Crohn's disease or ulcerative colitis, suggesting altered metabolism or excretion under these disease conditions. Storage conditions: The powder is stable for 3 years at -20°C and 2 years at 4°C; once dissolved, it can be stored for 6 months at -80°C and 1 month at -20°C.
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| Toxicity/Toxicokinetics |
As an endogenous bile acid, Allolithocholic acid maintains homeostasis at normal physiological concentrations through enterohepatic circulation and various regulatory mechanisms to prevent its accumulation in blood and tissues. However, high concentrations of bile acids exhibit potential toxic properties, primarily manifesting as disruptive effects on cell membranes (e.g., membrane disruption). In animal studies, administration of Allolithocholic acid (6 mg/kg) in rats induced hepatotoxic manifestations, including loss of microvilli in hepatocytes and dilation of canaliculi, which are hallmark pathological changes of cholestasis. At the cellular level, this compound exhibits cytotoxic effects on colon cancer cells at high concentrations. As a chemical reagent, this product is for research use only and not for human or veterinary use. IARC, ACGIH, NTP, and OSHA do not classify any component of this product as a human carcinogen. It should be handled by technically qualified persons following standard laboratory practices.
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| References | |
| Additional Infomation |
Allolithocholic acid is a type of bile acid.
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| Molecular Formula |
C24H40O3
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| Molecular Weight |
376.57
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| Exact Mass |
376.298
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| Elemental Analysis |
C, 76.55; H, 10.71; O, 12.75
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| CAS # |
2276-94-0
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| Related CAS # |
Lithocholic acid;434-13-9
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| PubChem CID |
5283803
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| Appearance |
White to off-white solid powder
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| Vapour Pressure |
1.4E-12mmHg at 25°C
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| LogP |
5.507
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
574
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| Defined Atom Stereocenter Count |
9
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| SMILES |
C[C@H](CCC(=O)O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC[C@@H]4[C@@]3(CC[C@H](C4)O)C)C
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| InChi Key |
SMEROWZSTRWXGI-NWFSOSCSSA-N
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| InChi Code |
InChI=1S/C24H40O3/c1-15(4-9-22(26)27)19-7-8-20-18-6-5-16-14-17(25)10-12-23(16,2)21(18)11-13-24(19,20)3/h15-21,25H,4-14H2,1-3H3,(H,26,27)/t15-,16+,17-,18+,19-,20+,21+,23+,24-/m1/s1
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| Chemical Name |
(4R)-4-[(3R,5S,8R,9S,10S,13R,14S,17R)-3-hydroxy-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 |
Allolithocholic acid; 2276-94-0; Cholan-24-oic acid,3-hydroxy-, (3a,5a)-; (4R)-4-[(3R,5S,8R,9S,10S,13R,14S,17R)-3-hydroxy-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; 3alpha-Hydroxy-5alpha-cholan-24-oic Acid; 3a-Hydroxy-5a-cholanoic acid; 3alpha-Hydroxy-5alpha-cholan-24-oic Acid ; (3alpha,5alpha)-3-Hydroxycholan-24-oic Acid ; 3alpha-Hydroxy-5alpha-cholanoic Acid ; (R)-4-((3R,5S,8R,9S,10S,13R,14S,17R)-3-Hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic Acid; SCHEMBL15156767;
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6555 mL | 13.2777 mL | 26.5555 mL | |
| 5 mM | 0.5311 mL | 2.6555 mL | 5.3111 mL | |
| 10 mM | 0.2656 mL | 1.3278 mL | 2.6555 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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