Endogenous Metabolite； nuclear receptors (FXR)

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].

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Inappropriate activation of the mineralocorticoid receptor (MR) results in renal sodium retention and potassium loss in patients with liver cirrhosis. Recent evidence suggested that this MR activation is, at least in part, a result of bile acid-dependent reduction in 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) activity, an enzyme preventing cortisol-dependent activation of MR by converting cortisol to cortisone. Here, we investigated the molecular mechanisms underlying bile acid-mediated MR activation. Analysis of urinary bile acids from 12 patients with biliary obstruction revealed highly elevated concentrations of chenodeoxycholic acid (CDCA), cholic acid (CA), and deoxycholic acid (DCA), with average concentrations of 50-80 microm. Although Chenodeoxycholic acid (CDCA) and DCA both mediated nuclear translocation of MR in the absence of 11 beta HSD2 and steroids in transiently expressing HEK-293 cells, the transcriptional activity of MR was not stimulated. In contrast, CDCA and DCA both inhibited 11 beta HSD2 with IC(50) values of 22 and 38 microm, respectively and caused cortisol-dependent nuclear translocation and increased transcriptional activity of MR. LCA, the bile acid that most efficiently inhibited 11 beta HSD2, was present at very low concentrations in cholestatic patients, whereas the weak inhibitor CA did not cause MR activation. In conclusion, these findings indicate that CDCA, and to a lesser extent DCA, by inhibiting 11 beta HSD2, mediate cortisol-dependent nuclear translocation and transcriptional activation of MR and are responsible at least for a part of the sodium retention and potassium excretion observed in patients with biliary obstruction.[1]

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Endometrial cancer exhibits a strong incidence in western developed countries mainly due to fat-rich diet and obesity. Processing of dietary lipids is triggered by bile acids, amphipathic detergents that are synthesized in the liver and stored in the gallbladder. In addition to their well-recognized role in dietary lipid absorption and cholesterol homeostasis, bile acids can also act as signaling molecules with systemic endocrine functions. In the present study we investigated the biological effects of the primary bile chenodeoxycholic acid (CDCA) on a human endometrial cancer cell line, Ishikawa. Low concentrations of CDCA are able to stimulate Ishikawa cell growth by inducing a significant increase in Cyclin D1 protein and mRNA expression through the activation of the membrane G protein-coupled receptor (TGR5)-dependent pathway. Dissecting the molecular mechanism underlying this effect by mutagenesis, EMSA and ChIP analysis revealed that CDCA-induced Cyclin D1 expression requires the enhanced recruitment of the transcription factor CREB on the cyclic AMP-responsive element motif within the Cyclin D1 gene proximal promoter. Our results suggest a novel molecular mechanism explaining the potential contribution of high-fat diet and obesity to endometrial cancer growth and progression opening the rationale for strategies to prevent the risk of this obesity-related cancer in women. [2]

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In a cultured human hepatoblastoma cell line, Hep G2, Chenodeoxycholic acid (CDCA) induced LDL receptor mRNA levels approximately 4 fold and mRNA levels for HMG-CoA reductase and HMG-CoA synthase two fold. In contrast, the mRNA levels for mevalonate kinase, farnesyl pyrophosphate synthase and squalene synthase were not changed significantly. The pattern of the induction of the sterol-sensitive genes was similar to the induction by N-acetyl-leucyl-leucyl-norleucinal (ALLN), an SREBP degradation inhibitor, suggesting that CDCA may increase mature SREBPs. CDCA could inhibit the 25-hydroxycholesterol mediated inactivation of SREBP without affecting mRNA levels of SREBPs. These results suggest that CDCA can affect sterol metabolism by a novel mechanism involving the inhibition of the oxysterol-mediated inactivation of SREBP. [3]

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High levels of Chenodeoxycholic acid (CDCA) and deoxycholic acid stimulate Cl(-) secretion in mammalian colonic epithelia. While different second messengers have been implicated in this action, the specific signaling pathway has not been fully delineated. Using human colon carcinoma T84 cells, we elucidated this cascade assessing Cl(-) transport by measuring I(-) efflux and short-circuit current (Isc). CDCA (500 μM) rapidly increases I(-) efflux, and we confirmed by Isc that it elicits a larger response when added to the basolateral vs. apical surface. However, preincubation with cytokines increases the monolayer responsiveness to apical addition by 55%. Nystatin permeabilization studies demonstrate that CDCA stimulates an eletrogenic apical Cl(-) but not a basolateral K(+) current. Furthermore, CDCA-induced Isc was inhibited (≥67%) by bumetanide, BaCl2, and the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh-172. CDCA-stimulated Isc was decreased 43% by the adenylate cyclase inhibitor MDL12330A and CDCA increases intracellular cAMP concentration. The protein kinase A inhibitor H89 and the microtubule disrupting agent nocodazole, respectively, cause 94 and 47% reductions in CDCA-stimulated Isc. Immunoprecipitation with CFTR antibodies, followed by sequential immunoblotting with Pan-phospho and CFTR antibodies, shows that CDCA increases CFTR phosphorylation by approximately twofold. The rapidity and side specificity of the response to CDCA imply a membrane-mediated process. While CDCA effects are not blocked by the muscarinic receptor antagonist atropine, T84 cells possess transcript and protein for the bile acid G protein-coupled receptor TGR5. These results demonstrate for the first time that CDCA activates CFTR via a cAMP-PKA pathway involving microtubules and imply that this occurs via a basolateral membrane receptor. [4]

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Farnesoid X receptor (FXR) regulates redox homeostasis and elicits a cytoprotective effect. CCAAT/enhancer binding protein-β (C/EBPβ) plays a role in regulating the expression of hepatocyte-specific genes and contributes to hepatocyte protection and liver regeneration. In view of the role of FXR in xenobiotic metabolism and hepatocyte survival, this study investigated the potential of FXR to activate C/EBPβ for the induction of detoxifying enzymes and the responsible regulatory pathway. Chenodeoxycholic acid (CDCA), a major component in bile acids, activates FXR. In HepG2 cells, CDCA treatment activated C/EBPβ, as shown by increases in its phosphorylation, nuclear accumulation, and expression. 3-(2,6-Dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl-)oxymethyl-5-isopropyl-isoxazole (GW4064), a synthetic FXR ligand, had similar effects. In addition, CDCA enhanced luciferase gene transcription from the construct containing -1.65-kb GSTA2 promoter, which contained C/EBP response element (pGL-1651). Moreover, CDCA treatment activated AMP-activated protein kinase (AMPK), which led to extracellular signal-regulated kinase 1/2 (ERK1/2) activation, as evidenced by the results of experiments using a dominant-negative mutant of AMPKα and chemical inhibitor. The activation of ERK1/2 was responsible for the activating phosphorylation of C/EBPβ. FXR knockdown attenuated the ability of CDCA to activate AMPK and ERK1/2 and phosphorylate C/EBPβ. Consistently, enforced expression of FXR promoted the phosphorylation of AMPKα, ERK1/2, and C/EBPβ, verifying that C/EBPβ phosphorylation elicited by CDCA results from the activation of AMPK and ERK1/2 by FXR. In mice, CDCA treatment activated C/EBPβ with the induction of detoxifying enzymes in the liver. Our results demonstrate that CDCA induces antioxidant and xenobiotic-metabolizing enzymes by activating C/EBPβ through AMPK-dependent ERK1/2 pathway downstream of FXR [5].

Rats treated with Chenodeoxycholic acid (CDCA) developed increased blood pressure, and adrenalectomized rats treated with CDCA showed enhanced renal sodium retention and urinary potassium excretion.11ß-hydroxysteroid dehydrogenase (11β-HSD) metabolizes active glucocorticoids to their inactive 11-dehydro products and protects renal mineralocorticoid receptors from the high circulating levels of endogenous glucocorticoids. 11ß-HSD has been suggested to be important not only in the control of renal sodium retention but also blood pressure. We had previously shown that 1α- and 11ß-hydroxyprogesterone (11α- and 11ß-OHP) were (I) potent inhibitors of 11ß-HSD (Isoforms 1 and 2) activity in vitro, (ii) able to confer mineralocorticoid (MC) activity upon corticosterone (B) in vivo and (iii) hypertensinogenic when chronically infused into Sprague-Dawley (SD) rats. In addition we also showed that 3α,5B-tetrahydroprogesterone (3α,5B-THP) and chenodeoxycholic acid (CDCA) were potent inhibitors of 11ß-HSD1 activity but not 11ß-HSD2 activity, however, these substances were still able to confer MC activity upon B in the adrenalectomized rat. To assess the possible blood pressure modulating effects of 3α,5B-THP and CDCA we have now infused these substances into intact SD rats continuously for 14 days. Both 3α,5B-THP and CDCA caused a significant elevation in blood pressure within seven days, an effect that persisted throughout the 14-day infusion. These results show that both 3α,5B-THP and CDCA are hypertensinogenic in the rat and that the inhibition of either 11ß-HSD2 or 11ß-HSD1 activity by endogenous progesterone metabolites and CDCA may be involved in the pathology of hypertension. https://www.tandfonline.com/doi/abs/10.1080/07435809609043778

Determination of 11βHSD2 Activity and Inhibition by Bile Acids [1]
11βHSD2 enzyme activity was measured in cell lysates as described. Briefly, transfected HEK-293 cells, incubated in charcoal-treated Dulbecco's modified Eagle's medium for 24 h, were washed once with Hanks' solution and resuspended in a buffer containing 100 mm NaCl, 1 mm MgCl2, 1 mm EDTA, 1 mm EGTA, 250 mmsucrose, 20 mm Tris-HCl, pH 7.4. Cells were lysed by freezing in liquid nitrogen. Dehydrogenase activity was measured in a final volume of 20 μl containing the appropriate concentration of bile acid, 30 nCi of [3H]cortisol, and unlabeled cortisol to a final concentrations of 50 nm. The reaction was started by mixing cell lysate with the reaction mixture. Alternatively, endoplasmic reticulum microsomes were prepared from transfected HEK-293 cells according to a procedure described previously and incubated with reaction mixture containing various concentrations of cortisol and Chenodeoxycholic acid (CDCA). Incubation proceeded for 20 min, and the conversion of cortisol to cortisone was determined by thin layer chromatography (TLC). Because of the inaccuracy of the TLC method at low conversion rates and the end-product inhibition of 11βHSD2 at conversion rates higher than 60–70%, only conversion rates between 10 and 60% were considered for calculation. The inhibitory constant IC50 was evaluated using the curve-fitting program. Results are expressed as means ± S.E. and consist of at least four independent measurements.
To determine whether 11βHSD2 metabolizes Chenodeoxycholic acid (CDCA), supernatants from cultures of HEK-293 cells transiently expressing 11βHSD2 were analyzed by gas chromatography-mass spectrometry. As a recovery standard 4 μg of 23-nor-deoxycholic acid was added to 1 ml of cell culture supernatant, and the sample was extracted on a Sep-Pak C18 column. To this extract 4 μg of 5β-cholestan-3β-ol was added as a standard for derivatization and gas chromatography, and the sample was derivatized to form the methylester trimethylsilyl ether. The excess of silylating agent was removed by gel filtration on a Lipidx-5000 column. Samples were analyzed by gas chromatography-mass spectrometry using a Hewlett Packard gas chromatograph 6890 equipped with a mass selective detector 5973 by selected ion monitoring (SIM, programmed for 5 different bile acids) and in the scan mode to detect any potentially new metabolite formed from Chenodeoxycholic acid (CDCA).

Iodide effluxes. [4]
Iodide efflux studies were performed as we have described earlier and are based on the original method of Venglarik et al. modified by Chappe et al. Briefly, T84 cells were grown in six-well plates. One million cells were seeded per well, and it took 4–5 days for the cells to reach 90% confluence at which time they were incubated with iodide loading buffer [containing in mM: 136 NaI, 3 KNO3, 2 Ca(NO3)2, 11 glucose, and 20 HEPES pH 7.4] for 1 h at room temperature in the dark. The cells were then rinsed three times with iodide-free efflux buffer (same as the iodide loading buffer except NaNO3 replaced NaI). Individual wells were exposed to DMSO, Chenodeoxycholic acid (CDCA) (500 μM), TCDC (500 μM), or a cAMP cocktail composed of 100 μM 8-Br-cAMP + 10 μM forskolin + 100 μM IBMX. Efflux buffer (1 ml) was then added to the dish; after 2 min, the buffer was removed and saved and another 1 ml fresh efflux buffer was added into each well. Samples were thus collected at 2-min intervals for the duration of the experiment. The iodide concentration of the collected samples was determined using an iodide-sensitive electrode and a pH/mV meter. The iodide concentration of samples were calculated based on a standard curve as previously described and depicted as the iodide efflux rate (nmol/min) at every 2-min intervals.

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Immunoprecipitation and immunoblot analysis. [4]
Immunoprecipitation and immunoblot analysis were conducted according to Sakesena et al. The cells were subjected to a growth and treatment regimen similar to that used for the Ussing chamber experiments. Briefly, T84 cells were seeded at a density of 1.5 × 106 cells per insert in six-well Transwell tissue culture inserts. When TER reached values of ≥950 Ω·cm2 (∼9–14 days) as determined by EVOM2 voltohmmeter and STX2 electrode, the cells were treated basolaterally with DMSO (0.1%), Chenodeoxycholic acid (CDCA) (500 μM), or forskolin (10 μM) for 20 min. Cells were washed three times with PBS, and the membrane was cut and immersed in lysis buffer (20 mM Tris·HCl pH 7.5, 150 mM NaCl, 1% Triton X-100, 1 mM EDTA, 1 mM EGTA, protease inhibitor cocktail, and phosphatase inhibitor cocktail 2). Cells from four wells were pooled together as one sample. The cells were sonicated on ice (25 s). The homogenate was centrifuged (1,000 g for 10 min at 4°C) to pellet out the nuclei and unbroken cells. The supernatant containing 5 mg protein was incubated with 3 μg monoclonal anti-human CFTR COOH-terminal antibody overnight at 4°C on a shaker. After incubation, immune complexes were precipitated using the protein A/G plus-agarose immunoprecipitation reagent.

3α, 5β-THP and bile acids were also tested to determine whether, like GA, they could confer mineralocorticoid actions upon corticosterone (B). In adrenalectomized rats pretreated with Chenodeoxycholic acid (CDCA) or 3α,5β-THP, B caused a significant antinatriuresis; the effect of B plus CDCA was blocked by the antimeneralocorticoid, RU 28318. Thus we report on two structurally similar endogenous substance, 3α, 5β-THP and CDCA, which inhibit both 11β-OHSD and 5β-R activity, and which can confer mineralocorticoid upon the glucococorticoid, B. (Steroids 59: 352–356, 1994), https://www.sciencedirect.com/science/article/abs/pii/0039128X94900019

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).

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10133 rat LD50 oral 4 gm/kg BEHAVIORAL: CHANGES IN MOTOR ACTIVITY (SPECIFIC ASSAY); LUNGS, THORAX, OR RESPIRATION: DYSPNEA; GASTROINTESTINAL: HYPERMOTILITY, DIARRHEA Oyo Yakuri. Pharmacometrics., 15(915), 1978
10133 rat LD50 intraperitoneal 105 mg/kg BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY); GASTROINTESTINAL: OTHER CHANGES; SKIN AND APPENDAGES (SKIN): HAIR: OTHER Oyo Yakuri. Pharmacometrics., 15(915), 1978
10133 rat LD50 subcutaneous >4 gm/kg BLOOD: CHANGES IN SPLEEN; SKIN AND APPENDAGES (SKIN): HAIR: OTHER Kiso to Rinsho. Clinical Report., 11(2499), 1977
10133 rat LD50 intravenous 106 mg/kg BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY); BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD; BEHAVIORAL: ATAXIA Oyo Yakuri. Pharmacometrics., 15(915), 1978
10133 rat LD50 intramuscular >500 mg/kg Drugs in Japan, -(397), 1990

[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

C, 73.43; H, 10.27; O, 16.30

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; Chenodiol; 474-25-9; Chenix; Chenic acid; Cdca; Chenodeoxycholate; 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.)