Natural Product (NP) Details

General Information of the NP (ID: NP8128)
Name
Rhein
Synonyms
Rhein; 478-43-3; Monorhein; Rheic acid; Rhubarb Yellow; Cassic acid; 4,5-Dihydroxyanthraquinone-2-carboxylic acid; 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid; Chrysazin-3-carboxylic acid; 1,8-Dihydroxy-3-carboxyanthraquinone; Rheinic acid; NSC 38629; 1,8-Dihydroxyanthraquinone-3-carboxylic acid; MFCD00009618; 2-Anthracenecarboxylic acid, 9,10-dihydro-4,5-dihydroxy-9,10-dioxo-; UNII-YM64C2P6UX; 4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid; 9,10-Dihydro-4,5-dihydroxy-9,10-dioxo-2-anthracenecarboxylic acid; Rhein (1,8-dihydroxy-3-carboxyl anthraquinone); 9,10-Dihydro-4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid; YM64C2P6UX; MLS000069639; CHEBI:8825; 2-Anthroic acid, 9,10-dihydro-4,5-dihydroxy-9,10-dioxo-; 4,5-Dihydroxy-2-anthraquinonecarboxylic acid; 4,5-DiOH-anthraquinone-2-COOH; SMR000058210; ST057726; dipropionyl rhein; 1,8-DIHYDROXY-3-CARBOXYL ANTHRAQUINONE; 9,10-Dihydro-4,5-dihydroxy-9,10-dioxo-2-anthroic acid; Rhein(Monorhein); CCRIS 5129; C15H8O6; EINECS 207-521-4; BRN 2222155; Rhein - Monorhein; RHN; Rhein,(S); Rhein; Rhubarb Yellow; Rhein, technical grade; 4ie7; ACMC-209kan; regid855879; Rhein-[13C6]; DSSTox_CID_6000; Rhein, analytical standard; 1,8-dihydroxy-3-carboxyl-9,10-anthraquinone; DSSTox_RID_77984; DSSTox_GSID_26000; SCHEMBL25253; US9238626, Rhein; 4-10-00-04088 (Beilstein Handbook Reference); cid_10168; MLS006011744; CHEMBL418068; MEGxp0_001866; 4,5-dihydroxy-9,10-dioxo-anthracene-2-carboxylic acid; DTXSID4026000; ACon1_000217; BDBM32021; ACT03257; BCP28202; HY-N0105; NSC38629; ZINC4098704; Tox21_201098; ANW-30573; BBL009695; CR0016; LMPK13040015; NSC-38629; s2400; SBB001152; STL141046; AKOS005259272; AC-7978; ACN-035339; CS-5239; DB13174; MCULE-1248137705; NCGC00018199-01; NCGC00018199-02; NCGC00018199-03; NCGC00018199-04; NCGC00018199-05; NCGC00018199-06; NCGC00018199-07; NCGC00023342-03; NCGC00023342-04; NCGC00258650-01; AK-88490; AM807834; AS-11635; CAS-478-43-3; SY051290; AB0010467; DB-014981; D3986; FT-0645050; FT-0674401; N1810; 4, 5-Dihydroxyanthraquinone-2-carboxylic acid; 2-Anthraquinonecarboxylic acid, 4,5-dihydroxy-; 78R433; C10401; X-4365; Q720356; Q-100512; 4,5-dihydroxy-9,10-dioxo-2-anthracenecarboxylic acid; BRD-K27335680-001-01-9; 2-Anthroic acid,10-dihydro-4,5-dihydroxy-9,10-dioxo-; 4,5-dihydroxy-9,10-diketo-anthracene-2-carboxylic acid; 2-Anthracenecarboxylic acid,10-dihydro-4,5-dihydroxy-9,10-dioxo-; 2-Anthroic acid, 9,10-dihydro-4,5-dihydroxy-9,10-dioxo- (8CI); 4,5-bis(oxidanyl)-9,10-bis(oxidanylidene)anthracene-2-carboxylic acid; 4,5-Dihydroxy-9,10-dioxo-9,10-dihydro-2-anthracenecarboxylic acid #; 9,10-Dihydro-4,5-dihydroxy-9,10-dioxo-2-anthracene carboxylic acid; 9,10-Dihydro-4,5-dihydroxy-9,10-dioxo-2-anthracenecarboxylic acid, 9CI
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Species Origin Rheum palmatum ...     Click to Show/Hide
Rheum palmatum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Caryophyllales
Family: Polygonaceae
Genus: Rheum
Species: Rheum palmatum
Disease Colitis [ICD-11: 1A40] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.187
 
MDCK Permeability
 -4.738
 
PAMPA
 +++
 
HIA
 - -
 
Distribution
VDss
 -0.784
 
PPB
 97.8%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 +
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 - - -
 
Excretion
CLplasma
 1.699
 
T1/2
 1.543
Toxicity
DILI
 +++
 
Rat Oral Acute Toxicity
 +
 
FDAMDD
 - -
 
Respiratory
 ++
 
Human Hepatotoxicity
 ++
 
Ototoxicity
 +
 
Drug-induced Nephrotoxicity
 ++
 
Drug-induced Neurotoxicity
 - -
 
Hematotoxicity
 ++
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C15H8O6
PubChem CID
10168
Canonical SMILES
C1=CC2=C(C(=C1)O)C(=O)C3=C(C2=O)C=C(C=C3O)C(=O)O
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)
InChIKey
FCDLCPWAQCPTKC-UHFFFAOYSA-N
CAS Number
CAS CAS 478-43-3
ChEBI ID
CHEBI:8825
Herb ID
HBIN042199
SymMap ID
SMIT00146
TCMSP ID
MOL002268
TTD Drug ID
D0M2TY
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Calphostin c      Breast cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
RKO CVCL_0504 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Rottlerin sensitizes colon carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via uncoupling of the mitochondria independent of protein kinase C.
Target and Pathway
Target(s) Heat shock protein 90 alpha (HSP90A)  Molecule Info  [3]
KEGG Pathway Protein processing in endoplasmic reticulum Click to Show/Hide
2 PI3K-Akt signaling pathway
3 Antigen processing and presentation
4 NOD-like receptor signaling pathway
5 Progesterone-mediated oocyte maturation
6 Estrogen signaling pathway
7 Pathways in cancer
8 Prostate cancer
NetPath Pathway IL2 Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
Pathway Interaction Database Signaling events mediated by HDAC Class II Click to Show/Hide
2 Validated targets of C-MYC transcriptional activation
3 Integrin-linked kinase signaling
4 LKB1 signaling events
5 Regulation of Telomerase
6 Glucocorticoid receptor regulatory network
7 Class I PI3K signaling events
8 IL2 signaling events mediated by PI3K
9 Regulation of Androgen receptor activity
10 Integrins in angiogenesis
11 Hypoxic and oxygen homeostasis regulation of HIF-1-alpha
12 ErbB receptor signaling network
13 VEGFR1 specific signals
14 Signaling events mediated by VEGFR1 and VEGFR2
15 Class I PI3K signaling events mediated by Akt
Reactome Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants Click to Show/Hide
2 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
3 Regulation of actin dynamics for phagocytic cup formation
4 eNOS activation
5 Regulation of PLK1 Activity at G2/M Transition
6 Attenuation phase
7 HSF1-dependent transactivation
8 Loss of Nlp from mitotic centrosomes
9 Recruitment of mitotic centrosome proteins and complexes
10 Loss of proteins required for interphase microtubule organization?from the centrosome
11 EPHA-mediated growth cone collapse
12 VEGFA-VEGFR2 Pathway
13 VEGFR2 mediated vascular permeability
14 Anchoring of the basal body to the plasma membrane
15 Constitutive Signaling by EGFRvIII
WikiPathways NRF2 pathway Click to Show/Hide
2 Nuclear Receptors Meta-Pathway
3 Aryl Hydrocarbon Receptor Pathway
4 Binding and Uptake of Ligands by Scavenger Receptors
5 Signaling by ERBB2
6 Fcgamma receptor (FCGR) dependent phagocytosis
7 Influenza Life Cycle
8 EBV LMP1 signaling
9 Aryl Hydrocarbon Receptor
10 Corticotropin-releasing hormone
11 TNF alpha Signaling Pathway
12 Arylhydrocarbon receptor (AhR) signaling pathway
13 Signaling by EGFR
14 Semaphorin interactions
15 Mitotic G2-G2/M phases
16 Metabolism of nitric oxide
17 NOD pathway
References
Reference 1 Rhein modulates host purine metabolism in intestine through gut microbiota and ameliorates experimental colitis. Theranostics. 2020 Aug 29;10(23):10665-10679.
Reference 2 Rottlerin sensitizes colon carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via uncoupling of the mitochondria independent of protein kinase C. Cancer Res. 2003 Aug 15;63(16):5118-25.
Reference 3 In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
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