Emodin
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Basic Info
| Common Name | Emodin(F04999) |
| 2D Structure | |
| Description | Emodin is found in dock. Emodin is present in Cascara sagrada.Emodin is a purgative resin from rhubarb, Polygonum cuspidatum, the buckthorn and Japanese Knotweed (Fallopia japonica). The term may also refer to any one of a series of principles isomeric with the emodin of rhubarb. (Wikipedia) Emodin has been shown to exhibit anti-inflammatory, signalling, antibiotic, muscle building and anti-angiogenic functions (A3049, A7853, A7854, A7855, A7857). |
| FRCD ID | F04999 |
| CAS Number | 518-82-1 |
| PubChem CID | 3220 |
| Formula | C15H10O5 |
| IUPAC Name | 1,3,8-trihydroxy-6-methylanthracene-9,10-dione |
| InChI Key | RHMXXJGYXNZAPX-UHFFFAOYSA-N |
| InChI | InChI=1S/C15H10O5/c1-6-2-8-12(10(17)3-6)15(20)13-9(14(8)19)4-7(16)5-11(13)18/h2-5,16-18H,1H3 |
| Canonical SMILES | CC1=CC(=C2C(=C1)C(=O)C3=CC(=CC(=C3C2=O)O)O)O |
| Isomeric SMILES | CC1=CC(=C2C(=C1)C(=O)C3=CC(=CC(=C3C2=O)O)O)O |
| Wikipedia | Emodin |
| Synonyms |
emodin
518-82-1
Schuttgelb
Emodol
Frangula emodin
Rheum emodin
Frangulic acid
3-Methyl-1,6,8-trihydroxyanthraquinone
Archin
Persian Berry Lake
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Anthracenes |
| Subclass | Anthraquinones |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Hydroxyanthraquinones |
| Alternative Parents | |
| Molecular Framework | Aromatic homopolycyclic compounds |
| Substituents | Hydroxyanthraquinone - Aryl ketone - 1-hydroxy-4-unsubstituted benzenoid - 1-hydroxy-2-unsubstituted benzenoid - Vinylogous acid - Ketone - Polyol - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Aromatic homopolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as hydroxyanthraquinones. These are compounds containing a hydroxyanthraquinone moiety, which consists of an anthracene bearing a quinone, and hydroxyl group. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 270.24 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 0 |
| Complexity | 434 |
| Monoisotopic Mass | 270.053 |
| Exact Mass | 270.053 |
| XLogP | 2.7 |
| Formal Charge | 0 |
| Heavy Atom Count | 20 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.5663 |
| Human Intestinal Absorption | HIA+ | 0.9878 |
| Caco-2 Permeability | Caco2+ | 0.7801 |
| P-glycoprotein Substrate | Substrate | 0.5422 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9619 |
| Non-inhibitor | 0.9432 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9058 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.8053 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7113 |
| CYP450 2D6 Substrate | Non-substrate | 0.8963 |
| CYP450 3A4 Substrate | Non-substrate | 0.6600 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.9107 |
| CYP450 2C9 Inhibitor | Inhibitor | 0.8825 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.6118 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.5367 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.5424 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.6156 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9449 |
| Non-inhibitor | 0.8974 | |
| AMES Toxicity | AMES toxic | 0.9108 |
| Carcinogens | Non-carcinogens | 0.8902 |
| Fish Toxicity | High FHMT | 0.9390 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9783 |
| Honey Bee Toxicity | High HBT | 0.6977 |
| Biodegradation | Not ready biodegradable | 0.7857 |
| Acute Oral Toxicity | III | 0.6654 |
| Carcinogenicity (Three-class) | Non-required | 0.6367 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.0170 | LogS |
| Caco-2 Permeability | 0.7805 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.5826 | LD50, mol/kg |
| Fish Toxicity | -0.0351 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.1847 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Development of a Method for Simultaneous Determination of Two Stilbenes and Four Anthraquinones from <i>Polygonum Cuspidatum</i> by RP-HPLC. | J AOAC Int | 2018 Jul 13 | 30005720 |
| Generation of Reactive Oxygen Species by Photosensitizers and their Modes ofAction on Proteins. | Curr Med Chem | 2018 Jan 4 | 29303072 |
| Aurantio-obtusin, an anthraquinone from cassiae semen, ameliorates lung inflammatory responses. | Phytother Res | 2018 Aug | 29675883 |
| Interaction of anthraquinones of <i>Cassia occidentalis</i> seeds with DNA and Glutathione. | Toxicol Rep | 2018 | 29326881 |
| Study on synthesis and bioactivity of biotinylated emodin. | Appl Microbiol Biotechnol | 2017 Jul | 28386632 |
| Emerging Mycotoxins: Beyond Traditionally Determined Food Contaminants. | J Agric Food Chem | 2017 Aug 23 | 27599910 |
| Polyphenols of Cassia tora leaves prevents lenticular apoptosis and modulatescataract pathology in Sprague-Dawley rat pups. | Biomed Pharmacother | 2016 Jul | 27261615 |
| Emodin improves lipid and glucose metabolism in high fat diet-induced obese mice through regulating SREBP pathway. | Eur J Pharmacol | 2016 Jan 5 | 26626587 |
| Promising Inhibitory Effects of Anthraquinones, Naphthopyrone, and NaphthaleneGlycosides, from Cassia obtusifolia on α-Glucosidase and Human Protein TyrosinePhosphatases 1B. | Molecules | 2016 Dec 27 | 28035984 |
| Activity-guided chemo toxic profiling of Cassia occidentalis (CO) seeds: detection of toxic compounds in body fluids of CO-exposed patients and experimental rats. | Chem Res Toxicol | 2015 Jun 15 | 25915165 |
| Evaluation of anti-diabetic and alpha glucosidase inhibitory action of anthraquinones from Rheum emodi. | Food Funct | 2015 Aug | 26145710 |
| Anti-inflammatory effect of emodin via attenuation of NLRP3 inflammasome activation. | Int J Mol Sci | 2015 Apr 10 | 25867480 |
| Quantitation of multiple mycotoxins and cyanogenic glucosides in cassava samples from Tanzania and Rwanda by an LC-MS/MS-based multi-toxin method. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2015 | 25350522 |
| Fungal and bacterial metabolites associated with natural contamination of locally processed rice (Oryza sativa L.) in Nigeria. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2015 | 25767914 |
| Effects of emodin and vitamin E on the growth and crowding stress of Wuchangbream (Megalobrama amblycephala). | Fish Shellfish Immunol | 2014 Oct | 25134848 |
| A survey of mycotoxins in domestic rice in Iran by liquid chromatography tandem mass spectrometry. | Toxicol Mech Methods | 2014 Jan | 24032669 |
| In vitro anti-osteoporosis properties of diverse Korean Drynariae rhizomaphenolic extracts. | Nutrients | 2014 Apr 24 | 24763116 |
| Emodin-6-O-β-D-glucoside inhibits HMGB1-induced inflammatory responses in vitro and in vivo. | Food Chem Toxicol | 2013 Feb | 23146691 |
| Isolation and identification of Flavobacterium columnare and Streptococcus iniae antibacterial compounds from the terrestrial plant Atraphaxis laetevirens. | J Agric Food Chem | 2012 Oct 24 | 23030835 |
| Effects of emodin and vitamin C on growth performance, biochemical parameters andtwo HSP70s mRNA expression of Wuchang bream (Megalobrama amblycephala Yih) under high temperature stress. | Fish Shellfish Immunol | 2012 May | 22281609 |
Targets
- General Function:
- Vitamin d 24-hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP1A1
- Uniprot ID:
- P04798
- Molecular Weight:
- 58164.815 Da
- Mechanism of Action:
- Emodin can induce the microsomal enzyme cytochrome P-450 1A1, perpetuating its own metabolic activation into genotoxic metabolites.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
- Gene Name:
- ESR2
- Uniprot ID:
- Q92731
- Molecular Weight:
- 59215.765 Da
- Mechanism of Action:
- Emodin has shown potent estrogen receptor binding affinity.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
- Specific Function:
- NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.
- Gene Name:
- NFKB2
- Uniprot ID:
- Q00653
- Molecular Weight:
- 96748.355 Da
- Mechanism of Action:
- Emodin can inhibit metastasis by interfering with the activity of matrix metalloproteinases, either directly or through through inhibition of focal adhesion kinase, mitogen-activated protein kinase, and RAC-alpha serine/threonine-protein kinase activation, and partial inhibition of transcription factor AP-1 and nuclear factor NF-kappa-B (NF-kB) transcriptional activities. Emodin's antiinflammatory action is also due to its specific inhibition of the transcription factor NF-kB.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Transcriptional repressor activity, rna polymerase ii transcription regulatory region sequence-specific binding
- Specific Function:
- NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105.
- Gene Name:
- NFKB1
- Uniprot ID:
- P19838
- Molecular Weight:
- 105355.175 Da
- Mechanism of Action:
- Emodin can inhibit metastasis by interfering with the activity of matrix metalloproteinases, either directly or through through inhibition of focal adhesion kinase, mitogen-activated protein kinase, and RAC-alpha serine/threonine-protein kinase activation, and partial inhibition of transcription factor AP-1 and nuclear factor NF-kappa-B (NF-kB) transcriptional activities. Emodin's antiinflammatory action is also due to its specific inhibition of the transcription factor NF-kB.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Transcription factor binding
- Specific Function:
- Participates in Wnt signaling (By similarity). Plays a complex role in regulating the basal catalytic activity of the alpha subunit.
- Gene Name:
- CSNK2B
- Uniprot ID:
- P67870
- Molecular Weight:
- 24942.25 Da
- Mechanism of Action:
- Emodin regulates angiogenesis by inhibiting the enzymes casein kinase II and nitric oxide synthase.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Rna polymerase ii carboxy-terminal domain kinase activity
- Specific Function:
- Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation.Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
- Gene Name:
- MAPK1
- Uniprot ID:
- P28482
- Molecular Weight:
- 41389.265 Da
- Mechanism of Action:
- Emodin can inhibit metastasis by interfering with the activity of matrix metalloproteinases, either directly or through through inhibition of focal adhesion kinase, mitogen-activated protein kinase, and RAC-alpha serine/threonine-protein kinase activation, and partial inhibition of transcription factor AP-1 and nuclear factor NF-kappa-B (NF-kB) transcriptional activities.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Tetrahydrobiopterin binding
- Specific Function:
- Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM.
- Gene Name:
- NOS2
- Uniprot ID:
- P35228
- Molecular Weight:
- 131116.3 Da
- Mechanism of Action:
- Emodin regulates angiogenesis by inhibiting the enzymes casein kinase II and nitric oxide synthase.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Transcriptional activator activity, rna polymerase ii transcription factor binding
- Specific Function:
- Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.
- Gene Name:
- JUN
- Uniprot ID:
- P05412
- Molecular Weight:
- 35675.32 Da
- Mechanism of Action:
- Emodin can inhibit metastasis by interfering with the activity of matrix metalloproteinases, either directly or through through inhibition of focal adhesion kinase, mitogen-activated protein kinase, and RAC-alpha serine/threonine-protein kinase activation, and partial inhibition of transcription factor AP-1 and nuclear factor NF-kappa-B (NF-kB) transcriptional activities.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Transcription regulatory region dna binding
- Specific Function:
- Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
- Gene Name:
- AHR
- Uniprot ID:
- P35869
- Molecular Weight:
- 96146.705 Da
References
- Zhang S, Qin C, Safe SH: Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context. Environ Health Perspect. 2003 Dec;111(16):1877-82. [14644660 ]
- General Function:
- Signal transducer activity
- Specific Function:
- Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.
- Gene Name:
- PTK2
- Uniprot ID:
- Q05397
- Molecular Weight:
- 119232.025 Da
- Mechanism of Action:
- Emodin can inhibit metastasis by interfering with the activity of matrix metalloproteinases, either directly or through through inhibition of focal adhesion kinase, mitogen-activated protein kinase, and RAC-alpha serine/threonine-protein kinase activation, and partial inhibition of transcription factor AP-1 and nuclear factor NF-kappa-B (NF-kB) transcriptional activities.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Can degrade fibrillar type I, II, and III collagens.
- Gene Name:
- MMP8
- Uniprot ID:
- P22894
- Molecular Weight:
- 53411.72 Da
- Mechanism of Action:
- Emodin can inhibit metastasis by interfering with the activity of matrix metalloproteinases, either directly or through through inhibition of focal adhesion kinase, mitogen-activated protein kinase, and RAC-alpha serine/threonine-protein kinase activation, and partial inhibition of transcription factor AP-1 and nuclear factor NF-kappa-B (NF-kB) transcriptional activities.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Serine-type endopeptidase activity
- Specific Function:
- Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.
- Gene Name:
- ELANE
- Uniprot ID:
- P08246
- Molecular Weight:
- 28517.81 Da
References
- Zembower DE, Kam CM, Powers JC, Zalkow LH: Novel anthraquinone inhibitors of human leukocyte elastase and cathepsin G. J Med Chem. 1992 May 1;35(9):1597-605. [1578486 ]
- General Function:
- Guanyl-nucleotide exchange factor activity
- Specific Function:
- Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.
- Gene Name:
- P2RY12
- Uniprot ID:
- Q9H244
- Molecular Weight:
- 39438.355 Da
References
- Baqi Y, Atzler K, Kose M, Glanzel M, Muller CE: High-affinity, non-nucleotide-derived competitive antagonists of platelet P2Y12 receptors. J Med Chem. 2009 Jun 25;52(12):3784-93. doi: 10.1021/jm9003297. [19463000 ]
- General Function:
- Protein tyrosine/serine/threonine phosphatase activity
- Specific Function:
- Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II.
- Gene Name:
- PTP4A3
- Uniprot ID:
- O75365
- Molecular Weight:
- 19534.69 Da
References
- Han YM, Lee SK, Jeong DG, Ryu SE, Han DC, Kim DK, Kwon BM: Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of PRL-3 phosphatase activity. Bioorg Med Chem Lett. 2012 Jan 1;22(1):323-6. doi: 10.1016/j.bmcl.2011.11.008. Epub 2011 Nov 9. [22137788 ]
- General Function:
- Protein serine/threonine/tyrosine kinase activity
- Specific Function:
- AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53.AKT1-specific substrates have been recently identified, including palladin (PALLD), which phosphorylation modulates cytoskeletal organization and cell motility; prohibitin (PHB), playing an important role in cell metabolism and proliferation; and CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation.
- Gene Name:
- AKT1
- Uniprot ID:
- P31749
- Molecular Weight:
- 55686.035 Da
- Mechanism of Action:
- Emodin can inhibit metastasis by interfering with the activity of matrix metalloproteinases, either directly or through through inhibition of focal adhesion kinase, mitogen-activated protein kinase, and RAC-alpha serine/threonine-protein kinase activation, and partial inhibition of transcription factor AP-1 and nuclear factor NF-kappa-B (NF-kB) transcriptional activities.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Exo-alpha-(2->8)-sialidase activity
- Specific Function:
- Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moities from glycoproteins, oligosaccharides and gangliosides.
- Gene Name:
- NEU2
- Uniprot ID:
- Q9Y3R4
- Molecular Weight:
- 42253.345 Da
References
- Arioka S, Sakagami M, Uematsu R, Yamaguchi H, Togame H, Takemoto H, Hinou H, Nishimura S: Potent inhibitor scaffold against Trypanosoma cruzi trans-sialidase. Bioorg Med Chem. 2010 Feb 15;18(4):1633-40. doi: 10.1016/j.bmc.2009.12.062. Epub 2010 Jan 6. [20097567 ]
- General Function:
- Protein serine/threonine kinase activity
- Specific Function:
- Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation. Plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue (PubMed:24962073).
- Gene Name:
- CSNK2A1
- Uniprot ID:
- P68400
- Molecular Weight:
- 45143.25 Da
- Mechanism of Action:
- Emodin regulates angiogenesis by inhibiting the enzymes casein kinase II and nitric oxide synthase.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
- Mechanism of Action:
- Emodin has shown potent estrogen receptor binding affinity.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]
- General Function:
- Sh2 domain binding
- Specific Function:
- Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.
- Gene Name:
- LCK
- Uniprot ID:
- P06239
- Molecular Weight:
- 58000.15 Da
- Mechanism of Action:
- Emodin is a strong inhibitor of tyrosine-protein kinase Lck and other tyrosine kinase receptors, which likely contributes to its growth suppressing activity.
References
- Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P: Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev. 2007 Sep;27(5):591-608. [17019678 ]