With IC50 values of 22 mM and 38 mM, respectively, chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) both block 11 beta HSD2, induce alcohol pivoting, and raise the regulatory activity of salt stress hormone (MR) [1]. By activating the membrane G protein-coupled receptor (TGR5), chelodeoxycholicacid can significantly boost the expression of cyclin D1 protein and mRNA, which in turn promotes the development of Ishikawa cells [2]. Chenodeoxycholic acid (CDCA) can decrease the mRNA levels of HMG-CoA reductase and HMG-CoA synthase and raise the level of LDL receptor mRNA by approximately four times in the cultured human hepatoblastoma cell line Hep G2 [3]. There were two level increases. Isc (≥67%) generated by chenodeoxycholic acid is inhibited by activation of CFTRinh-172 by bumetanide, BaCl2, and cystic fibrosis transmembrane conductance regulator (CFTR). The adenylyl cyclase mirror MDL12330A decreased chenodeoxycholic acid-stimulated Isc by 43%, but chenodeoxycholic acid raised intracellular cAMP concentration [4]. Treatment with chenodeoxycholic acid activates C/EBPβ, as evidenced by increased expression in HepG2 cells, phosphorylation, and nuclear accumulation. The 1.65-kb GSTA2 promoter with the C/EBP response element (pGL-1651) was used to control the chenodeoxycholic acid-enhanced luciferase gene. Experimental studies employing AMPKα dominant-negative mutants and chemical substitutions show that chenodeoxycholic acid therapy activates AMP-activated protein status (AMPK), which leads to activation of extracellular signaling regulator 1/2 (ERK1/2) [5].

Absorption, Distribution and Excretion
Chenodiol is well absorbed from the small intestine.
About 80% of its bacterial metabolite lithocholate is excreted in the feces.

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Metabolism / Metabolites
Chenodiol is well absorbed from the small intestine and taken up by the liver where it is converted to its taurine and glycine conjugates and secreted in bile. At steady-state, an amount of chenodiol near the daily dose escapes to the colon and is converted by bacterial action to lithocholic acid. About 80% of the lithocholate is excreted in the feces; the remainder is absorbed and converted in the liver to its poorly absorbed sulfolithocholyl conjugates. During chenodiol therapy there is only a minor increase in biliary lithocholate, while fecal bile acids are increased three- to fourfold.

Hepatotoxicity
In multiple clinical trials of chenodiol therapy for dissolution of gallstones, serum aminotransferase elevations occurred in up to 30% of patients. The elevations generally arose within 2 months of starting therapy and were typically mild, transient and not accompanied by symptoms or jaundice. Liver biopsies done during chenodiol therapy generally showed mild, nonspecific changes. Clinically apparent liver injury with jaundice was not reported. The liver enzyme elevations were generally dose related and usually did not recur on restarting chenodiol at lower doses. While the serum enzyme abnormalities that occurred on chenodiol therapy generated considerable concern, they appeared to be relatively benign. Since the approval of chenodiol and its more widespread use, at least four instances of liver injury with jaundice have been reported to the sponsor, but the clinical features and outcomes of these cases have not been published. Nevertheless, the product label for chenodiol includes a boxed warning about hepatotoxicity although it does not provide advice on the frequency or how to respond to abnormalities. Thus, the reliability of reports of clinically apparent liver injury with chenodiol therapy remains unclear. Once ursodiol was found to be equally as effective as chenodiol, even at lower doses, and was rarely associated with serum enzyme elevations, it rapidly replaced chenodiol as medical therapy for gallstones.
Likelihood score: E* (Suspected but unproven cause of clinically apparent liver injury).

[1]. Chenodeoxycholic acid and deoxycholic acid inhibit 11 beta-hydroxysteroid dehydrogenase type 2 and cause cortisol-induced transcriptional activation of the mineralocorticoid receptor. J Biol Chem. 2002 Jul 19;277(29):26286-92.

[2]. Chenodeoxycholic acid through a TGR5-dependent CREB signaling activation enhances cyclin D1 expression and promotes human endometrial cancer cell proliferation. Cell Cycle. 2012 Jul 15;11(14):2699-710.

[3]. The molecular mechanism of the induction of the low density lipoprotein receptor by chenodeoxycholic acid in cultured human cells. Biochem Biophys Res Commun. 1995 Mar 8;208(1):405-11.

[4]. Chenodeoxycholic acid stimulates Cl(-) secretion via cAMP signaling and increases cystic fibrosis transmembrane conductance regulator phosphorylation in T84 cells. Am J Physiol Cell Physiol. 2013 Aug 15;305(4):C447-56.

[5]. Farnesoid X receptor activation by chenodeoxycholic acid induces detoxifying enzymes through AMP-activated protein kinase and extracellular signal-regulated kinase 1/2-mediated phosphorylation of CCAAT/enhancer binding protein β. Drug Metab.

Chenodiol can cause developmental toxicity according to state or federal government labeling requirements.
Chenodeoxycholic acid is a dihydroxy-5beta-cholanic acid that is (5beta)-cholan-24-oic acid substituted by hydroxy groups at positions 3 and 7 respectively. It has a role as a human metabolite and a mouse metabolite. It is a bile acid, a dihydroxy-5beta-cholanic acid and a C24-steroid. It is a conjugate acid of a chenodeoxycholate.
Chenodeoxycholic acid (or Chenodiol) is an epimer of ursodeoxycholic acid (DB01586). Chenodeoxycholic acid is a bile acid naturally found in the body. It works by dissolving the cholesterol that makes gallstones and inhibiting production of cholesterol in the liver and absorption in the intestines, which helps to decrease the formation of gallstones. It can also reduce the amount of other bile acids that can be harmful to liver cells when levels are elevated.
Chenodeoxycholic acid (chenodiol) is a primary bile acid, synthesized in the liver and present in high concentrations in bile that is used therapeutically to dissolve cholesterol gallstones. Chronic therapy is associated with transient elevations in serum aminotransferase levels in up to 30% of patients, but chenodiol has been linked to only rare instances of clinically apparent liver injury with jaundice.
Chenodeoxycholic acid has been reported in Homo sapiens and Ganoderma lucidum with data available.
A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones.
See also: Sodium Chenodeoxycholate (is active moiety of).

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Drug Indication
Chenodiol is indicated for patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease or age. Chenodiol will not dissolve calcified (radiopaque) or radiolucent bile pigment stones.
FDA Label
Chenodeoxycholic acid is indicated for the treatment of inborn errors of primary bile acid synthesis due to sterol 27 hydroxylase deficiency (presenting as cerebrotendinous xanthomatosis (CTX)) in infants, children and adolescents aged 1 month to 18 years and adults.

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Mechanism of Action
Chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid in an expanded bile acid pool. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gall-bladder visualized by oral cholecystography. Bile acids may also bind the the bile acid receptor (FXR) which regulates the synthesis and transport of bile acids.

C24H40O4

392.58

392.292

474-25-9

Chenodeoxycholic Acid-d4;99102-69-9;Chenodeoxycholic acid-13C;52918-92-0;Chenodeoxycholic Acid-d9;Chenodeoxycholic acid-d5;52840-12-7

10133

White to off-white solid powder

1.1±0.1 g/cm3

547.1±25.0 °C at 760 mmHg

165-167 °C(lit.)

298.8±19.7 °C

0.0±3.3 mmHg at 25°C

1.543

4.66

3

4

4

28

605

10

C[C@H](CCC(=O)O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2[C@@H](C[C@H]4[C@@]3(CC[C@H](C4)O)C)O)C

RUDATBOHQWOJDD-BSWAIDMHSA-N

InChI=1S/C24H40O4/c1-14(4-7-21(27)28)17-5-6-18-22-19(9-11-24(17,18)3)23(2)10-8-16(25)12-15(23)13-20(22)26/h14-20,22,25-26H,4-13H2,1-3H3,(H,27,28)/t14-,15+,16-,17-,18+,19+,20-,22+,23+,24-/m1/s1

(4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-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

Anthropodesoxycholic acid Anthropodeoxycholic acid Chenodeoxycholic Acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~127.37 mM)
0.1 M NaOH : ~50 mg/mL (~127.37 mM)

Solubility in Formulation 1: 2.5 mg/mL (6.37 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.37 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.

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Solubility in Formulation 4: ≥ 20 mg/mL (50.95 mM) (saturation unknown) in 20% HP-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)