NAV
Explore a selection of essential drug information below, or:
Unlock enhanced features & extensive drug insights. Create a free account.
Explore the full scope of our drug knowledge tailored for pharmaceutical research needs in our data library. Learn more.

Rhein

Explore a selection of our essential drug information below, or:

CREATE FREE ACCOUNT
Full Drug Profiles
Unlock enhanced features & extensive drug insights, including detailed interaction data & regulatory status. Create a free account.
SUBSCRIBERECOMMENDED FOR PHARMA
Data Packages
Explore the full scope of our drug knowledge tailored for pharmaceutical research needs in our data library. Learn more.

Identification

Generic Name
Rhein
DrugBank Accession Number
DB13174
Background

Rhein is an anthraquinone metabolite of rheinanthrone and senna glycoside is present in many medicinal plants including Rheum palmatum, Cassia tora, Polygonum multiflorum, and Aloe barbadensis 1. It is known to have hepatoprotective, nephroprotective, anti-cancer, anti-inflammatory, and several other protective effects.

Type
Small Molecule
Groups
Experimental
Structure
3D
Similar Structures
Weight
Average: 284.2204
Monoisotopic: 284.032087988
Chemical Formula
C15H8O6
Synonyms
Not Available
External IDs
  • NSC-38629
Unlock the secrets to drugging the undruggable
Discover how groundbreaking research is turning "undruggable" targets into therapeutic opportunities.
Download eBook
Unlock the secrets to drugging the undruggable
Download eBook

Pharmacology

Indication

No approved indication.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

*Liver: *Reverses animal models of non-alcoholic fatty liver disease by lowering liver lipids and reducing inflammation 5. Also reverses and prevents fibrosis in liver injury 6.

*Kidney: *Protects against fibrosis in nephropathy models and improves epithelial tight junction function 7 9.

Bone and joint: Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity 1920 21.

Lipid lowering and anti-obesity: Reduces body weight and fat content, and lowers high density lipoprotein and low density lipoprotein 14. May prevent adipocyte differentiation 13.

Anti-oxidant/Pro-oxidant: Reduces levels of reactive oxygen species (ROS) at concentrations of about 2-16 microM but induces the generation of ROS at concentrations of 50 microM and above 15 16.

Anti-cancer: Rhein has been observed to produce DNA damage and suppress DNA repair in cancer cells 22. It induces apoptosis via ER stress, calcium, and mitochondria mediated pathways 23. Rhein also prevents cancer cell invasion into systemic circulation by preventing angiogenesis and breakdown of the extracellular matrix 24. Finally, rhein suppresses the activation of several tumor promoting signalling pathways 24 25 26.

*Anti-inflammatory: * Suppresses the production of pro-inflammatory cytokines such as interleukin-1beta and interleukin-6 19 20.

*Anti-diabetic: *Lowers plasma glucose and increases survival of islet beta cells in type 2 diabetes mellitus models 2.

Anti-microbial: Inhibits arylamine N-acteyltransferase and cell growth in Helicobacter pylori 11. Rhien also appears to be effective against many genotypes of Staphylococcus aureus 12.

Anti-allergenic: Inhibits production of leukotrienes and the release of histamine from mast cells 17.

Mechanism of action

*Liver: *The reversal of non-alcoholic fatty liver disease stems from rhien's lipid lowering and anti-obesity actions which result in an overall decrease in body weight, high density lipoprotein, and low density lipoprotein as well as its anti-inflammatory action 5. The reversal of hepatic fibrosis is thought to be due to rhien's anti-inflammatory and anti-oxidant action which suppresses the pro-fibrotic signalling from macrophages and further damage from reactive oxygen species respectively 6. Ultimately this results in reduced expression of alpha-smooth muscle actin (Alpha-SMA) which is indicative of decreased hepatic stellate cell and myofibroblast activation. Rhein also appears to suppress the expression of transforming growth factor-Beta (TGF-Beta)

*Kidney: *The protection from fibrosis in the kidney also appears to stem from rhien's anti-inflammatory action resulting in less inflammatory cell infiltration along with suppression of alpha-SMA and fibronectin expression 7. These indicate a reduction in the activation of interstitial fibroblasts which are responsible for excess production of extracellular matrix components. Rhien may also suppress TGF-beta expression in the kidney. The anti-fibrotic mechanism of rhien may involve the upregulation of bone morphogenetic protein 7 and hepatic growth factor 8. In diabetic nephropathy rhein appears to suppress the expression of integrin-linked kinase leading to a reduction in the matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 ratio 10. The improvement of epithelial tight junction function seems to involve upregulation of zona occludins protein-1 and occludin expression 9.

Bone and joint:Rhein reduces cartilage destruction by decreasing expression of matrix metalloproteinase (MMP)-1 and -3 as well as upregulating tissue inhibitor of matrix metalloproteinases which serve to reduce the activity of several MMPs 21. The anti-inflammatory action of rhein reduces the level of interleukin-1beta activity which plays a large role in reduction of extracellular matrix production, MMP activity, and continued inflammation 20. Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism 19.

*Lipid lowering and anti-obesity: *Rhein is known to bind and inhibit liver X receptor alpha and beta with Kd values of 46.7 microM and 31.97 microM respectively 14. This decreases the expression of genes such as that of sterol regulatory element binding transcription factor 1 (SREBP1c) and its downstream genes for fatty acid synthase (FAS), steroyl-coenzyme A desaturase 1 (SCD1), and acetyl CoA carboxylase 1 (ACC1). SREBP1c, FAS, SCD1, and ACC1 are all involved in adipogenesis and their suppression results in less fat content. The genes for ABCA1 and ABCG1 are also suppressed. These correspond to cholesterol efflux trasporters and likely explain the reductiion in HDL and LDL seen with rhein. The inhibition of LXR by rhien relieves the inhibition on uncoupling protein 1 expression in brown adipose tissue. The result of this is increased thermogenesis which likely plays a role in the reduction of body weight produced by rhien. Additionally, rhein may downregulate peroxisome proliferator-receptor gamma and its downstream genes to inhibit adipocyte differentiation 13.

Anti-oxidant/Pro-oxidant: The antoxidant mechanism is unknown. The pro-oxidant action of rhien may involve the inhibition of mitochondrial respiratory complex 1 and subsequent facilitation of NADH and NADPH dependent lipid peroxidation 16.

Anti-cancer: The exact mechanism of rhein's ability to damage DNA and supress the expression of DNA repair enzymes ADR and MGMT is unknown 22. The mechanism through which rhien induces ER stress is unknown but likely involves its pro-oxidant properties 23. Rhein has been observed to produce increases in cytosolic calcium, reductions in mitochondrial membrane potential, and upregulation of pro-apoptotic proteins as well as leakage of cytochrome C which would induce apoptosis via the intrinsic pathway. The reduction of matrix metalloproteinase-9 serves to prevent extra cellular matrix breakdown by cancer cells and hinders their invasion into surrounding tissue 24. Rhein also decreases vascular endothelial growth factor expression through an unknown mechanism to prevent cancer cells from stimulating agiogenesis. Rhein reduces the activity of the nuclear factor kappa (NFkappaB) pathway by preventing the destruction of IKBalpha 24 27. The activity of the phosphoinositol 3-kinase/Akt pathway is also reduced by rhien 25. Rhein's inhibition of the mitogen-activated protein kinase pathways (particularly those involving extracellular signal regulated kinase) appears to follow a U-shaped dose response curve. ERK phosphorylation is inhibited at low concentrations of around 3microM but activated at higher concentrations of around 30microM 26. Furthermore, ERK phosporylation is again inhibited at extremely high concentrations in excess of 100 microM 24. The suppression of these three pathways is likely involved in the anti-proliferative effects of rhein.

Anti-inflammatory: The mechanism of rhein's anti-inflammatory effect likely involves its inhibition of the NFkappa B pathway which plays a role in the production of many pro-inflammatory cytokines 24 27. Rhein's anti-oxidant activity may also play a role in preventing damage during inflammation.

Anti-diabetic: Rhein is thought to increase islet beta cell survival by suppressing the expression of dynamin-related protein 1 and thereby preventing mitochondrial fission 2. Rhein's anti-oxidant properties are also thought to play a role in protecting islet beta cells. The reduction in plasma glucose is likely due to increased survival of islet beta cells and subsequent increases in insulin secretion. Rhein's anti-inflammatory action may also serve to reduce insulin resistance.

Anti-microbial: Rhien inhibits H. pylori arylamine N-acetyltransferase in a dose dependent manner 11. The mechanism of rhein's anti-microbial effect on H. pylori and S. aureus are unknown.

Anti-allergenic: Rhien inhibits 5-lipoxygenase with an IC50 of 13.7microM 17. Rhien also inhibits mast cell degranulation although the specific mechanism is unknown.

TargetActionsOrganism
AHeat shock protein HSP 90-alpha
inhibitor
Humans
UOxysterols receptor LXR-alpha
inhibitor
Humans
UOxysterols receptor LXR-beta
inhibitor
Humans
UArylamine N-acetyltransferase
inhibitor
Helicobacter pylori
UPolyunsaturated fatty acid 5-lipoxygenase
inhibitor
Humans
Absorption

Tmax of 1.6-2.6 hours 3.

Volume of distribution

15-60L 3.

Protein binding

99% bound to plasma proteins 3.

Metabolism

Metabolized primarily to rhein glucuronide and rhien sulfate 3.

Route of elimination

37% is excreted in urine and 53% in feces as estimated in rats 4.

Half-life

4-10h 3.

Clearance

Total CL is 1.5 L/h and renal CL is 0.1 L/h 3.

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Oral LD50 of >5000mg/kg in mice MSDS.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Rhein.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Rhein.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Rhein.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Rhein.
AcetohexamideThe metabolism of Acetohexamide can be decreased when combined with Rhein.
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as anthracenecarboxylic acids. These are organic compounds containing a carboxylic acid group attached to an anthracene ring system.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Anthracenes
Sub Class
Anthracenecarboxylic acids and derivatives
Direct Parent
Anthracenecarboxylic acids
Alternative Parents
Anthraquinones / Naphthalenecarboxylic acids / Hydroxybenzoic acid derivatives / Aryl ketones / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides
show 1 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / 2-naphthalenecarboxylic acid / 2-naphthalenecarboxylic acid or derivatives / 9,10-anthraquinone / Anthracene carboxylic acid / Anthraquinone / Aromatic homopolycyclic compound / Aryl ketone / Carboxylic acid
show 9 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
anthracenes (CHEBI:8825) / Anthracenes and phenanthrenes, Anthraquinone type (C10401) / Anthracenes and phenanthrenes (LMPK13040015)
Affected organisms
  • Helicobacter pylori
  • Staphylococcus aureus

Chemical Identifiers

UNII
YM64C2P6UX
CAS number
478-43-3
InChI Key
FCDLCPWAQCPTKC-UHFFFAOYSA-N
InChI
InChI=1S/C15H8O6/c16-9-3-1-2-7-11(9)14(19)12-8(13(7)18)4-6(15(20)21)5-10(12)17/h1-5,16-17H,(H,20,21)
IUPAC Name
4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid
SMILES
OC(=O)C1=CC2=C(C(O)=C1)C(=O)C1=C(C=CC=C1O)C2=O

References

General References
  1. Zhou YX, Xia W, Yue W, Peng C, Rahman K, Zhang H: Rhein: A Review of Pharmacological Activities. Evid Based Complement Alternat Med. 2015;2015:578107. doi: 10.1155/2015/578107. Epub 2015 Jun 22. [Article]
  2. Liu J, Chen Z, Zhang Y, Zhang M, Zhu X, Fan Y, Shi S, Zen K, Liu Z: Rhein protects pancreatic beta-cells from dynamin-related protein-1-mediated mitochondrial fission and cell apoptosis under hyperglycemia. Diabetes. 2013 Nov;62(11):3927-35. doi: 10.2337/db13-0251. Epub 2013 Aug 6. [Article]
  3. Nicolas P, Tod M, Padoin C, Petitjean O: Clinical pharmacokinetics of diacerein. Clin Pharmacokinet. 1998 Nov;35(5):347-59. [Article]
  4. De Witte P, Lemli J: Excretion and distribution of [14C]rhein and [14C]rhein anthrone in rat. J Pharm Pharmacol. 1988 Sep;40(9):652-5. [Article]
  5. Sheng X, Wang M, Lu M, Xi B, Sheng H, Zang YQ: Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice. Am J Physiol Endocrinol Metab. 2011 May;300(5):E886-93. doi: 10.1152/ajpendo.00332.2010. Epub 2011 Mar 1. [Article]
  6. Guo MZ, Li XS, Xu HR, Mei ZC, Shen W, Ye XF: Rhein inhibits liver fibrosis induced by carbon tetrachloride in rats. Acta Pharmacol Sin. 2002 Aug;23(8):739-44. [Article]
  7. He D, Lee L, Yang J, Wang X: Preventive effects and mechanisms of rhein on renal interstitial fibrosis in obstructive nephropathy. Biol Pharm Bull. 2011;34(8):1219-26. [Article]
  8. Su J, Yin LP, Zhang X, Li BB, Liu L, Li H: Chronic allograft nephropathy in rats is improved by the intervention of rhein. Transplant Proc. 2013 Jul-Aug;45(6):2546-52. doi: 10.1016/j.transproceed.2013.03.030. [Article]
  9. Peng SN, Zeng HH, Fu AX, Chen XW, Zhu QX: Effects of rhein on intestinal epithelial tight junction in IgA nephropathy. World J Gastroenterol. 2013 Jul 14;19(26):4137-45. doi: 10.3748/wjg.v19.i26.4137. [Article]
  10. Peng L, Yang J, Ning C, Zhang J, Xiao X, He D, Wang X, Li Z, Fu S, Ning J: Rhein inhibits integrin-linked kinase expression and regulates matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio in high glucose-induced epithelial-mesenchymal transition of renal tubular cell. Biol Pharm Bull. 2012;35(10):1676-85. [Article]
  11. Chung JG, Tsou MF, Wang HH, Lo HH, Hsieh SE, Yen YS, Wu LT, Chang SH, Ho CC, Hung CF: Rhein affects arylamine N-acetyltransferase activity in Helicobacter pylori from peptic ulcer patients. J Appl Toxicol. 1998 Mar-Apr;18(2):117-23. [Article]
  12. Yu L, Xiang H, Fan J, Wang D, Yang F, Guo N, Jin Q, Deng X: Global transcriptional response of Staphylococcus aureus to rhein, a natural plant product. J Biotechnol. 2008 Jun 30;135(3):304-8. doi: 10.1016/j.jbiotec.2008.04.010. Epub 2008 Apr 29. [Article]
  13. Liu Q, Zhang XL, Tao RY, Niu YJ, Chen XG, Tian JY, Ye F: Rhein, an inhibitor of adipocyte differentiation and adipogenesis. J Asian Nat Prod Res. 2011 Aug;13(8):714-23. doi: 10.1080/10286020.2011.586341. [Article]
  14. Sheng X, Zhu X, Zhang Y, Cui G, Peng L, Lu X, Zang YQ: Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue. Int J Biol Sci. 2012;8(10):1375-84. doi: 10.7150/ijbs.4575. Epub 2012 Oct 29. [Article]
  15. Zhong XF, Huang GD, Luo T, Deng ZY, Hu JN: Protective effect of rhein against oxidative stress-related endothelial cell injury. Mol Med Rep. 2012 May;5(5):1261-6. doi: 10.3892/mmr.2012.793. Epub 2012 Feb 16. [Article]
  16. Glinn MA, Lee CP, Ernster L: Pro- and anti-oxidant activities of the mitochondrial respiratory chain: factors influencing NAD(P)H-induced lipid peroxidation. Biochim Biophys Acta. 1997 Jan 16;1318(1-2):246-54. [Article]
  17. Singh B, Nadkarni JR, Vishwakarma RA, Bharate SB, Nivsarkar M, Anandjiwala S: The hydroalcoholic extract of Cassia alata (Linn.) leaves and its major compound rhein exhibits antiallergic activity via mast cell stabilization and lipoxygenase inhibition. J Ethnopharmacol. 2012 May 7;141(1):469-73. doi: 10.1016/j.jep.2012.03.012. Epub 2012 Mar 17. [Article]
  18. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
  19. Pelletier JP, Lajeunesse D, Reboul P, Mineau F, Fernandes JC, Sabouret P, Martel-Pelletier J: Diacerein reduces the excess synthesis of bone remodeling factors by human osteoblast cells from osteoarthritic subchondral bone. J Rheumatol. 2001 Apr;28(4):814-24. [Article]
  20. Moldovan F, Pelletier JP, Jolicoeur FC, Cloutier JM, Martel-Pelletier J: Diacerhein and rhein reduce the ICE-induced IL-1beta and IL-18 activation in human osteoarthritic cartilage. Osteoarthritis Cartilage. 2000 May;8(3):186-96. [Article]
  21. Tamura T, Kosaka N, Ishiwa J, Sato T, Nagase H, Ito A: Rhein, an active metabolite of diacerein, down-regulates the production of pro-matrix metalloproteinases-1, -3, -9 and -13 and up-regulates the production of tissue inhibitor of metalloproteinase-1 in cultured rabbit articular chondrocytes. Osteoarthritis Cartilage. 2001 Apr;9(3):257-63. [Article]
  22. Chen YY, Chiang SY, Lin JG, Yang JS, Ma YS, Liao CL, Lai TY, Tang NY, Chung JG: Emodin, aloe-emodin and rhein induced DNA damage and inhibited DNA repair gene expression in SCC-4 human tongue cancer cells. Anticancer Res. 2010 Mar;30(3):945-51. [Article]
  23. Hsia TC, Yang JS, Chen GW, Chiu TH, Lu HF, Yang MD, Yu FS, Liu KC, Lai KC, Lin CC, Chung JG: The roles of endoplasmic reticulum stress and Ca2+ on rhein-induced apoptosis in A-549 human lung cancer cells. Anticancer Res. 2009 Jan;29(1):309-18. [Article]
  24. Lin ML, Chung JG, Lu YC, Yang CY, Chen SS: Rhein inhibits invasion and migration of human nasopharyngeal carcinoma cells in vitro by down-regulation of matrix metalloproteinases-9 and vascular endothelial growth factor. Oral Oncol. 2009 Jun;45(6):531-7. doi: 10.1016/j.oraloncology.2008.07.012. Epub 2008 Sep 18. [Article]
  25. Fernand VE, Losso JN, Truax RE, Villar EE, Bwambok DK, Fakayode SO, Lowry M, Warner IM: Rhein inhibits angiogenesis and the viability of hormone-dependent and -independent cancer cells under normoxic or hypoxic conditions in vitro. Chem Biol Interact. 2011 Jul 15;192(3):220-32. doi: 10.1016/j.cbi.2011.03.013. Epub 2011 Mar 30. [Article]
  26. Aviello G, Rowland I, Gill CI, Acquaviva AM, Capasso F, McCann M, Capasso R, Izzo AA, Borrelli F: Anti-proliferative effect of rhein, an anthraquinone isolated from Cassia species, on Caco-2 human adenocarcinoma cells. J Cell Mol Med. 2010 Jul;14(7):2006-14. doi: 10.1111/j.1582-4934.2009.00815.x. Epub 2009 Jun 16. [Article]
  27. Mendes AF, Caramona MM, de Carvalho AP, Lopes MC: Diacerhein and rhein prevent interleukin-1beta-induced nuclear factor-kappaB activation by inhibiting the degradation of inhibitor kappaB-alpha. Pharmacol Toxicol. 2002 Jul;91(1):22-8. [Article]
Human Metabolome Database
HMDB0032876
KEGG Compound
C10401
PubChem Compound
10168
PubChem Substance
347829278
ChemSpider
9762
BindingDB
32021
ChEBI
8825
ChEMBL
CHEMBL418068
ZINC
ZINC000004098704
PDBe Ligand
RHN
Wikipedia
Rhein_(molecule)
PDB Entries
3r2a / 4ie7 / 4rfr
MSDS
Download (77.2 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Unlock 175K+ rows when you subscribe.View sample data

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)>300MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.214 mg/mLALOGPS
logP2.18ALOGPS
logP3.27Chemaxon
logS-3.1ALOGPS
pKa (Strongest Acidic)3.4Chemaxon
pKa (Strongest Basic)-5.6Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area111.9 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity72.37 m3·mol-1Chemaxon
Polarizability26.62 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-07cv-0590000000-afcf37d77e69652177f2
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-0090000000-9ac3e7791e49a21d3f7e
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000i-0090000000-8a0c3c4f77482fc05626
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000i-0190000000-a217257577bda56ddeb9
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-0950000000-f5cac5a3a6c78fc4ed85
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-0910000000-4671892dc0bcf7214bc0
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-000i-0090000000-5f27d9cb7d81c2b3da8d
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-000i-0190000000-87c468c6073faf9e5fae
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-001i-0920000000-0b0038f124d8c1494117
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0090000000-a2294fd7666d75dbcbd0
MS/MS Spectrum - , positiveLC-MS/MSsplash10-052u-0890000000-5f1951e9414e26b22db9
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0090000000-505b1f3a9d95ffdff2f7
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00kr-0090000000-5e2272090985a5895f11
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0090000000-5b189b9592f5ab4604cf
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-030r-0490000000-79d2705aaf8b7dede9fb
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0090000000-158978f61feb5902ae37
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0190000000-eb18dd4b6d96e2107c9d
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-172.5790026
predicted
DarkChem Lite v0.1.0
[M-H]-172.6954026
predicted
DarkChem Lite v0.1.0
[M-H]-172.8097026
predicted
DarkChem Lite v0.1.0
[M-H]-158.53404
predicted
DeepCCS 1.0 (2019)
[M+H]+174.0940026
predicted
DarkChem Lite v0.1.0
[M+H]+174.3264026
predicted
DarkChem Lite v0.1.0
[M+H]+175.4919026
predicted
DarkChem Lite v0.1.0
[M+H]+160.89204
predicted
DeepCCS 1.0 (2019)
[M+Na]+173.3724026
predicted
DarkChem Lite v0.1.0
[M+Na]+173.4864026
predicted
DarkChem Lite v0.1.0
[M+Na]+173.0394026
predicted
DarkChem Lite v0.1.0
[M+Na]+167.43324
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. Heat shock protein HSP 90-alpha
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812)
Specific Function
ATP binding
Gene Name
HSP90AA1
Uniprot ID
P07900
Uniprot Name
Heat shock protein HSP 90-alpha
Molecular Weight
84659.015 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Details2. Oxysterols receptor LXR-alpha
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:19481530, PubMed:25661920, PubMed:37478846). Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES (PubMed:37478846). LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides (By similarity). Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (PubMed:19481530). Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (By similarity). Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles. Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (By similarity)
Specific Function
cholesterol binding
Gene Name
NR1H3
Uniprot ID
Q13133
Uniprot Name
Oxysterols receptor LXR-alpha
Molecular Weight
50395.34 Da
References
  1. Sheng X, Zhu X, Zhang Y, Cui G, Peng L, Lu X, Zang YQ: Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue. Int J Biol Sci. 2012;8(10):1375-84. doi: 10.7150/ijbs.4575. Epub 2012 Oct 29. [Article]
Details3. Oxysterols receptor LXR-beta
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920). Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (By similarity). Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (By similarity). Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957)
Specific Function
apolipoprotein A-I receptor binding
Gene Name
NR1H2
Uniprot ID
P55055
Uniprot Name
Oxysterols receptor LXR-beta
Molecular Weight
50973.375 Da
References
  1. Sheng X, Zhu X, Zhang Y, Cui G, Peng L, Lu X, Zang YQ: Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue. Int J Biol Sci. 2012;8(10):1375-84. doi: 10.7150/ijbs.4575. Epub 2012 Oct 29. [Article]
4. Arylamine N-acetyltransferase
Kind
Group
Organism
Helicobacter pylori
Pharmacological action
Unknown
Actions
Inhibitor
References
  1. Chung JG, Tsou MF, Wang HH, Lo HH, Hsieh SE, Yen YS, Wu LT, Chang SH, Ho CC, Hung CF: Rhein affects arylamine N-acetyltransferase activity in Helicobacter pylori from peptic ulcer patients. J Appl Toxicol. 1998 Mar-Apr;18(2):117-23. [Article]
Details5. Polyunsaturated fatty acid 5-lipoxygenase
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:19022417, PubMed:21233389, PubMed:22516296, PubMed:23246375, PubMed:24282679, PubMed:24893149, PubMed:31664810, PubMed:8615788, PubMed:8631361). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:17114001, PubMed:21206090, PubMed:31664810, PubMed:32404334, PubMed:8615788). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity)
Specific Function
arachidonate 12(S)-lipoxygenase activity
Gene Name
ALOX5
Uniprot ID
P09917
Uniprot Name
Polyunsaturated fatty acid 5-lipoxygenase
Molecular Weight
77982.595 Da
References
  1. Singh B, Nadkarni JR, Vishwakarma RA, Bharate SB, Nivsarkar M, Anandjiwala S: The hydroalcoholic extract of Cassia alata (Linn.) leaves and its major compound rhein exhibits antiallergic activity via mast cell stabilization and lipoxygenase inhibition. J Ethnopharmacol. 2012 May 7;141(1):469-73. doi: 10.1016/j.jep.2012.03.012. Epub 2012 Mar 17. [Article]

Enzymes

Details1. Cytochrome P450 1A2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function
aromatase activity
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58406.915 Da
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
Details2. Cytochrome P450 3A Subfamily (Protein Group)
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Components:
NameUniProt ID
Cytochrome P450 3A4P08684
Cytochrome P450 3A43Q9HB55
Cytochrome P450 3A5P20815
Cytochrome P450 3A7P24462
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
Details3. Cytochrome P450 2E1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
Specific Function
4-nitrophenol 2-monooxygenase activity
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
Details4. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Enzyme action is based on in vitro data.
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]
  2. Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Yiap BC, Ong CE: Cytochrome P450 2C9-natural antiarthritic interactions: Evaluation of inhibition magnitude and prediction from in vitro data. Biopharm Drug Dispos. 2018 Apr;39(4):205-217. doi: 10.1002/bdd.2127. Epub 2018 Mar 23. [Article]
Details5. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [Article]

Drug created at May 19, 2017 14:56 / Updated at October 10, 2024 16:27