Natural Product (NP) Details

General Information of the NP (ID: NP0060)
Name
Norcantharidin
Synonyms
Norcantharidin; 5442-12-6; 29745-04-8; 7-Oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride; Endothall anhydride; 4,7-Epoxyisobenzofuran-1,3-dione, hexahydro-; NCTD; 3,6-Endoxohexahydrophthalic anhydride; (+/-)-NCTD; 7-Oxabicyclo(2.2.1)heptane-2,3-dicarboxylic anhydride; Norcantharadine; (+/-)-Norcantharidin; Hexahydro-4,7-epoxyisobenzofuran-1,3-dione; 4,10-dioxatricyclo[5.2.1.02,6]decane-3,5-dione; 4,10-dioxatricyclo[5.2.1.0<2,6>]decane-3,5-dione; exo-7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride; DEMETHYL-CANTHARIDIN; Isocantharidin; MFCD00213361; 3, hexahydro-; NSC 14003; Norcantharidin, solid; Spectrum_001667; 3,6-Endooxyphthalic anhydride, hexahydro-; SpecPlus_000904; Phthalic anhydride, hexahydro-3,6-endoxo-; 4,3-dione, hexahydro-; Spectrum2_001683; Spectrum3_001634; Spectrum4_000601; Spectrum5_001514; CHEMBL8327; Lopac0_000830; BSPBio_003327; KBioGR_001122; KBioSS_002147; Phthalic anhydride,6-endoxo-; MLS002153470; DivK1c_007000; SCHEMBL177729; SPECTRUM1504153; SPBio_001606; KBio1_001944; KBio2_002147; KBio2_004715; KBio2_007283; KBio3_002547; DTXSID30884158; HMS3262F21; HMS3370H07; 4,7-Epoxyisobenzofuran-1,3-dione; BCP09826; BCP25426; HY-N0585; NSC14003; NSC59023; Tox21_500830; WLN: T C555 A AO DVOVTJ; CCG-39454; NSC-14003; NSC-59023; NSC148536; s3759; SBB005955; STK424286; Hexahydro-3,6-epoxyphthalic anhydride; AKOS003267901; FS-4623; LP00830; MCULE-7561066553; NSC-148536; SDCCGSBI-0050807.P003; NCGC00015756-03; NCGC00015756-04; NCGC00015756-05; NCGC00015756-06; NCGC00015756-07; NCGC00015756-08; NCGC00015756-09; NCGC00015756-14; NCGC00094161-01; NCGC00094161-02; NCGC00094161-03; NCGC00094161-04; NCGC00094161-05; NCGC00094161-06; NCGC00261515-01; NCI60_001019; SMR000326693; ST057264; DB-050518; CS-0009119; EU-0100830; FT-0614776; FT-0621477; FT-0626378; N1662; hexahydro-4,7-epoxy-2-benzofuran-1,3-dione; N 8784; 3,6-Endoxohexahydrophthalic anhydride, exo isomer; SR-01000076037; SR-01000076037-1; 4,10-dioxatricyclo[5.2.1.0?,?]decane-3,5-dione; BRD-A66914119-001-04-0; Q15425762; 4,10-Dioxa-tricyclo[5.2.1.02,6]decane-3,5-dione; 3-(5'-(4-(diphenylamino)phenyl)-[2,2'-bithiophen]-5-yl)cyclohex-2-enone; EXO-7-OXA-BICYCLO(2.2.1)-HEPTANE-2,3-DICARBOXYLIC ANHYDRIDE; Exo-cis-Hexahydro-4,7-epoxyisobenzofuran-1,3-dione; Endothall anhydride; 51154-98-4; TIMTEC-BB SBB005955;4,7-Epoxyisobenzofuran-1,3-dione, hexahydro-;4,10-Dioxatricyclo[5.2.1.0(2,6)]decane-3,5-dione
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Species Origin Epicauta pensylvanica ...     Click to Show/Hide
Epicauta pensylvanica
Kingdom: Metazoa
Phylum: Arthropoda
Class: Insecta
Order: Coleoptera
Family: Meloidae
Genus: Epicauta
Species: Epicauta pensylvanica
Disease Renal fibrosis [ICD-11: MF54] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.63
 
MDCK Permeability
 -4.601
 
PAMPA
 +++
 
HIA
 ++
 
Distribution
VDss
 -0.192
 
PPB
 8.7%
 
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
 1.065
 
T1/2
 2.848
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
C8H8O4
PubChem CID
93004
Canonical SMILES
C1CC2C3C(C1O2)C(=O)OC3=O
InChI
1S/C8H8O4/c9-7-5-3-1-2-4(11-3)6(5)8(10)12-7/h3-6H,1-2H2
InChIKey
JAABVEXCGCXWRR-UHFFFAOYSA-N
CAS Number
CAS 5442-12-6
Herb ID
HBIN037307
SymMap ID
SMIT04210
TCMSP ID
MOL001857
TTD Drug ID
D0W4IL
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Crizotinib      Lung 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 Phosphorylation MET  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
                    In-vitro Model MHCC97-H CVCL_4972 Adult hepatocellular carcinoma Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model For a xenograft model, 2*106 human HepG2 cells were injected subcutaneously into the right flanks of the mice into the right flanks of the mice.
                    Experimental
                    Result(s)		 Cytotoxic autophagy resulting from inhibition of c-Met/mTOR signaling may be achieved in HCC by combined NCTD and crizotinib administration.
Target and Pathway
Target(s) Phosphatase 2A PR61alpha (PPP2R5A)  Molecule Info  [3]
Serine/threonine PP1-alpha (PPP1CA)  Molecule Info  [4]
KEGG Pathway mRNA surveillance pathway Click to Show/Hide
2 Sphingolipid signaling pathway
3 Oocyte meiosis
4 PI3K-Akt signaling pathway
5 AMPK signaling pathway
6 Adrenergic signaling in cardiomyocytes
7 Dopaminergic synapse
Panther Pathway EGF receptor signaling pathway Click to Show/Hide
2 FGF signaling pathway
3 Wnt signaling pathway
Pathway Interaction Database Canonical Wnt signaling pathway Click to Show/Hide
2 C-MYC pathway
3 Validated transcriptional targets of deltaNp63 isoforms
Reactome Degradation of beta-catenin by the destruction complex Click to Show/Hide
2 Separation of Sister Chromatids
3 Resolution of Sister Chromatid Cohesion
4 CTLA4 inhibitory signaling
5 Platelet sensitization by LDL
6 Disassembly of the destruction complex and recruitment of AXIN to the membrane
7 S33 mutants of beta-catenin aren't phosphorylated
8 S37 mutants of beta-catenin aren't phosphorylated
9 S45 mutants of beta-catenin aren't phosphorylated
10 T41 mutants of beta-catenin aren't phosphorylated
11 RHO GTPases Activate Formins
12 RAF activation
13 Negative regulation of MAPK pathway
14 Mitotic Prometaphase
WikiPathways Glycogen Metabolism Click to Show/Hide
References
Reference 1 Norcantharidin protects against renal interstitial fibrosis by suppressing TWEAK-mediated Smad3 phosphorylation. Life Sci. 2020 Nov 1;260:118488.
Reference 2 Norcantharidin alone or in combination with crizotinib induces autophagic cell death in hepatocellular carcinoma by repressing c-Met-mTOR signaling. Oncotarget. 2017 Dec 4;8(70):114945-114955.
Reference 3 Structure-activity relationship of cantharidin derivatives to protein phosphatases 1, 2A1, and 2B, Bioorg. Med. Chem. Lett. 7(14):1833-1836 (1997).
Reference 4 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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