Natural Product (NP) Details

General Information of the NP (ID: NP8519)
Name
Cepharanthine
Synonyms
Cepharanthin; (+)-Cepharanthine; O-Methylcepharanoline; Cepharantin; Cepharanthine [JAN]; UNII-7592YJ0J6T; 6',12'-Dimethoxy-2,2'-dimethyl-6,7-(methylenebis(oxy))oxyacanthan; CHEBI:3546; 7592YJ0J6T; NSC623442; Cepharanthine (JAN); ecaene (non-preferred name); DSSTox_CID_25957; DSSTox_RID_81253; DSSTox_GSID_45957; C37H38N2O6; NSC-623442; CAS-481-49-2; CCRIS 6539; SR-01000779734; NSC 623442; BRN 0075231; Cepharanthin,(S); NCGC00095194-01; (14S,27R)-22,33-dimethoxy-13,28-dimethyl-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2~16,19~.1~3,10~.1~21,25~.0~4,8~.0~14,39~.0~31,35~]nonatriaconta-1(33),3,8,10(39),16,18,21(36),22,24,31,34,37-dod; Cepharanthine (TN); Spectrum2_000832; Spectrum3_001963; 12-O-Methylcepharanoline; UPCMLD-DP054; BSPBio_003563; 4-27-00-09061 (Beilstein Handbook Reference); MLS000728518; SCHEMBL154545; SPECTRUM1505322; SPBio_000783; CHEMBL449782; DTXSID6045957; UPCMLD-DP054:001; KBio3_002909; Cepharanthine, >=95% (HPLC); Cepharanthine, >=98% (HPLC); HMS1922J12; HMS2232F21; Pharmakon1600-01505322; HY-N6972; Tox21_111483; BBL030154; BDBM50423643; CCG-40294; MFCD00210482; NSC758965; s4238; STK801907; ZINC30726863; AKOS004119865; Oxyacanthan, 6',12'-dimethoxy-2,2'-dimethyl-6,7-(methylenebis(oxy))-; Tox21_111483_1; MCULE-4243165865; NSC-758965; SDCCGMLS-0066893.P001; NCGC00161621-01; NCGC00161621-02; NCGC00161621-03; NCGC00161621-05; NCGC00161621-13; AC-15206; AK168069; AS-17451; SMR000445632; SBI-0207049.P001; CS-0007138; V0178; C09391; D01035; AB00643356_08; AB00643356_09; 481C492; Q-100524; SR-01000779734-3; SR-01000779734-4; BRD-K96194081-001-06-0; Q15410888; 6',12'-Dimethoxy-2,2'-dimethyl-6,7-[methylenebis-(oxy)]oxyacanthan; Oxyacanthan, 6',12'-dimethoxy-2,2'-dimethyl-6,7-(methylenebis(oxy))- (9CI); (14S,27R)-22,33-dimethoxy-13,28-dimethyl-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),16,18,21(36),22,24,31,34,37-dodecaene; (14S,27R)-22,33-dimethoxy-13,28-dimethyl-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2??,??.1?,??.1??,??.0?,?.0??,??.0??,??]nonatriaconta-1(33),3,8,10(39),16,18,21(36),22,24,31,34,37-dodecaene
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Species Origin Stephania delavayi ...     Click to Show/Hide
Stephania delavayi
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Menispermaceae
Genus: Stephania
Species: Stephania delavayi
Disease Hepatocellular carcinoma [ICD-11: 2C12] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.705
 
MDCK Permeability
 -4.741
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 0.445
 
PPB
 80.7%
 
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
 7.389
 
T1/2
 2.247
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
C37H38N2O6
PubChem CID
10206
Canonical SMILES
CN1CCC2=CC3=C(C4=C2C1CC5=CC=C(C=C5)OC6=C(C=CC(=C6)CC7C8=CC(=C(C=C8CCN7C)OC)O4)OC)OCO3
InChI
1S/C37H38N2O6/c1-38-13-11-24-18-31(41-4)33-20-27(24)28(38)16-23-7-10-30(40-3)32(17-23)44-26-8-5-22(6-9-26)15-29-35-25(12-14-39(29)2)19-34-36(37(35)45-33)43-21-42-34/h5-10,17-20,28-29H,11-16,21H2,1-4H3/t28-,29+/m1/s1
InChIKey
YVPXVXANRNDGTA-WDYNHAJCSA-N
CAS Number
CAS 481-49-2
Herb ID
HBIN020124
SymMap ID
SMIT00671
TCMSP ID
MOL006973
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          S-1      Gastrointestinal stromal tumor     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 DPYD  Molecule Info 
Pathway MAP
Down-regulation Expression TYMS  Molecule Info 
Pathway MAP
                    In-vitro Model HSC-2 CVCL_1287 Oral cavity squamous cell carcinoma Homo sapiens
B88 Oral squamous cell carcinoma Homo sapiens
                    In-vivo Model B88 or HSC2 cells (1*106) were suspended in 0.1 mL of serum-free medium and injected into the subcutaneous tissue of 5-week-old nude mice.
                    Experimental
                    Result(s)		 Combined therapy of cepharanthine and S-1 exerted antitumor effects on human OSCC xenografts markedly and significantly induced apoptotic cells in tumors treated with cepharanthine plus S-1.
Target and Pathway
Target(s) Cathepsin B (CTSB)  Molecule Info  [3]
Cathepsin D (CTSD)  Molecule Info  [3]
Eukaryotic translation initiation factor 2A (MYO1C)  Molecule Info  [4]
Eukaryotic translation initiation factor 5A-1-like (NPC1)  Molecule Info  [5]
BioCyc Thyroid hormone biosynthesis Click to Show/Hide
KEGG Pathway Sphingolipid signaling pathway Click to Show/Hide
2 Lysosome
3 Tuberculosis
4 Antigen processing and presentation
NetPath Pathway IL2 Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
Pathway Interaction Database LKB1 signaling events Click to Show/Hide
2 Ceramide signaling pathway
3 Direct p53 effectors
4 Validated nuclear estrogen receptor alpha network
Reactome Collagen degradation Click to Show/Hide
2 Metabolism of Angiotensinogen to Angiotensins
3 MHC class II antigen presentation
4 Trafficking and processing of endosomal TLR
5 Assembly of collagen fibrils and other multimeric structures
References
Reference 1 Cepharanthine hydrochloride induces mitophagy targeting GPR30 in hepatocellular carcinoma (HCC). Expert Opin Ther Targets. 2020 Apr;24(4):389-402.
Reference 2 Effects of cepharanthine alone and in combination with fluoropyrimidine anticancer agent, S-1, on tumor growth of human oral squamous cell carcinoma xenografts in nude mice. Anticancer Res. 2009 Apr;29(4):1263-70.
Reference 3 Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell?lung cancer. Cancer Lett. 2018 Jan 1;412:1-9.
Reference 4 Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network. J Exp Clin Cancer Res. 2019 Nov 7;38(1):457.
Reference 5 Pharmacological blockade of cholesterol trafficking by cepharanthine in endothelial cells suppresses angiogenesis and tumor growth. Cancer Lett. 2017 Nov 28;409:91-103.
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