CAS 474-25-9|Chenodeoxycholic acid

Introduction：Basic information about CAS 474-25-9|Chenodeoxycholic acid, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Chenodeoxycholic acid BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Customs
7. Articles130
8. Synonyms

Common Name	Chenodeoxycholic acid
CAS Number	474-25-9	Molecular Weight	392.572
Density	1.1±0.1 g/cm3	Boiling Point	547.1±25.0 °C at 760 mmHg
Molecular Formula	C₂₄H₄₀O₄	Melting Point	165-167 °C(lit.)
MSDS	ChineseUSA	Flash Point	298.8±19.7 °C
Symbol	GHS07	Signal Word	Warning

Names

Name	chenodeoxycholic acid
Synonym	More Synonyms

Chenodeoxycholic acid BiologicalActivity

Description	Chenodeoxycholic Acid is a hydrophobic primary bile acid that activates nuclear receptors (FXR) involved in cholesterol metabolism.
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>FXRNatural Products >>Acids and AldehydesResearch Areas >>Metabolic Disease
Target	Human Endogenous Metabolite
In Vitro	Chenodeoxycholic acid (CDCA) and Deoxycholic acid (DCA) both inhibit 11 beta HSD2 with IC50 values of 22 mM and 38 mM, respectively and causes cortisol-dependent nuclear translocation and increases transcriptionalactivity of mineralocorticoid receptor (MR)[1]. Chenodeoxycholic acid is 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[2]. Chenodeoxycholic acid (CDCA) induces LDL receptor mRNA levels approximately 4 fold and mRNA levels for HMG-CoA reductase and HMG-CoA synthase two fold in a cultured human hepatoblastoma cell line, Hep G2[3]. Chenodeoxycholic acid-induced Isc is inhibited (≥67%) by Bumetanide, BaCl2, and the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh-172. Chenodeoxycholic acid-stimulated Isc is decreased 43% by the adenylate cyclase inhibitor MDL12330A and Chenodeoxycholic acid increases intracellular cAMP concentration[4]. Chenodeoxycholic acid treatment activates C/EBPβ, as shown by increases in its phosphorylation, nuclear accumulation, and expression in HepG2 cells. Chenodeoxycholic acid enhances luciferase gene transcription from the construct containing -1.65-kb GSTA2 promoter, which contains C/EBP response element (pGL-1651). Chenodeoxycholic acid treatment activates AMP-activated protein kinase (AMPK), which leads 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[5].
Kinase Assay	Briefly, transfected HEK-293 cells, incubated in charcoal-treated Dulbecco's modified Eagle's medium for 24 h, are 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 are lysed by freezing in liquid nitrogen. Dehydrogenase activity is 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 is started by mixing cell lysate with the reaction mixture. Alternatively, endoplasmic reticulum microsomes are prepared from transfected HEK-293 cells and incubated with reaction mixture containing various concentrations of cortisol and CDCA. Incubation proceeded for 20 min, and the conversion of cortisol to cortisone is 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% are considered for calculation. The inhibitory constant IC50 is evaluated using the curve-fitting program. Results are expressed as means±S.E. and consist of at least four independent measurements.
Cell Assay	The cell viability is analyzed by incubating transfected HEK-293 cells and CHO cells for 1 h with the corresponding concentration of bile acid and staining with trypan blue. The toxicity of bile acids is analyzed using the tetrazolium salt MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) according to the cell proliferation kit I. No significant differences between control and bile acid-treated cells are obtained in both tests.
References	[1]. Stauffer AT, et al. 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]. Casaburi I, et al. 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]. Kawabe Y, et al. 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]. Ao M, et al. 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]. Noh K, et al. 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

Chemical & Physical Properties

Density	1.1±0.1 g/cm3
Boiling Point	547.1±25.0 °C at 760 mmHg
Melting Point	165-167 °C(lit.)
Molecular Formula	C₂₄H₄₀O₄
Molecular Weight	392.572
Flash Point	298.8±19.7 °C
Exact Mass	392.292664
PSA	77.76000
LogP	4.66
Vapour Pressure	0.0±3.3 mmHg at 25°C
Index of Refraction	1.543
InChIKey	RUDATBOHQWOJDD-BSWAIDMHSA-N
SMILES	CC(CCC(=O)O)C1CCC2C3C(O)CC4CC(O)CCC4(C)C3CCC12C
Water Solubility	PRACTICALLY INSOLUBLE

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: FZ1980000

CHEMICAL NAME :: 5-beta-Cholan-24-oic acid, 3-alpha,7-alpha-dihydroxy-

CAS REGISTRY NUMBER :: 474-25-9

LAST UPDATED :: 199806

DATA ITEMS CITED :: 30

MOLECULAR FORMULA :: C24-H40-O4

MOLECULAR WEIGHT :: 392.64

WISWESSER LINE NOTATION :: L E5 B666TJ A1 E1 FY1&2VQ KQ OQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4 gm/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 105 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - other changes Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >4 gm/kg

TOXIC EFFECTS :: Blood - changes in spleen Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 106 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >500 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 86 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >4 gm/kg

TOXIC EFFECTS :: Gastrointestinal - ulceration or bleeding from small intestine Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 100 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 500 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3750 mg/kg/30D-C

TOXIC EFFECTS :: Endocrine - changes in adrenal weight Related to Chronic Data - changes in prostate weight Related to Chronic Data - changes in testicular weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 45500 mg/kg/26W-C

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 18200 mg/kg/52W-C

TOXIC EFFECTS :: Liver - other changes Liver - changes in liver weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 24 gm/kg/5Y-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 100 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1785 mg/kg

SEX/DURATION :: female 4-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - hepatobiliary system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 550 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Effects on Newborn - physical

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1375 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3480 mg/kg

SEX/DURATION :: female 15-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 14820 mg/kg

SEX/DURATION :: female 31 week(s) pre-mating female 1-24 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - hepatobiliary system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1500 mg/kg

SEX/DURATION :: female 21-45 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - hepatobiliary system Reproductive - Specific Developmental Abnormalities - endocrine system Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1500 mg/kg

SEX/DURATION :: female 21-45 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - physical

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 260 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

MUTATION DATA

TYPE OF TEST :: DNA adduct

TEST SYSTEM :: Mammal - species unspecified Lymphocyte

DOSE/DURATION :: 10 mg/L

REFERENCE :: CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 15,1911,1994

Safety Information

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H315-H319
Precautionary Statements	P305 + P351 + P338
Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
Hazard Codes	Xn:Harmful
Risk Phrases	R63
Safety Phrases	S22-S24/25-S45-S36/37
RIDADR	NONH for all modes of transport
WGK Germany	2
RTECS	FZ1980000
HS Code	2918990090

Customs

HS Code	2918990090
Summary	2918990090. other carboxylic acids with additional oxygen function and their anhydrides, halides, peroxides and peroxyacids; their halogenated, sulphonated, nitrated or nitrosated derivatives. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Articles130

Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Intermediates of the Cholesterol Biosynthetic Pathway in Primary Cultured Rat Hepatocytes.

J. Pharmacol. Exp. Ther. 355 , 429-41, (2015)

Cytosolic sulfotransferase 1C2 (SULT1C2) is expressed in the kidney, stomach, and liver of rats; however, the mechanisms regulating expression of this enzyme are not known. We evaluated transcriptiona...

Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.

Chem. Res. Toxicol. 23 , 171-83, (2010)

Drug-induced liver injury is one of the main causes of drug attrition. The ability to predict the liver effects of drug candidates from their chemical structures is critical to help guide experimental...

Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).

J. Sci. Ind. Res. 65(10) , 808, (2006)

Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI typ...

Synonyms

CDCA

Chenix

MFCD00064142

Chenodex

EINECS 207-481-8

Hekbilin

Fluibil

Ulmenide

Chenocol

chendol

Kebilis

anthropododesoxycholicacid

Chenodeoxycholic acid

3α,7α-Dihydroxy-5β-cholanic Acid

Chendiol

5β-Cholanic Acid-3α,7α-diol

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