Natural Product (NP) Details

General Information of the NP (ID: NP7968)
Name
Deguelin
Synonyms
(-)-Deguelin; (-)-cis-deguelin; DEGUELIN(-); UNII-K5Z93K66IE; CHEBI:4357; K5Z93K66IE; MFCD01740600; C23H22O6; (7as,13as)-13,13a-dihydro-9,10-dimethoxy-3,3-dimethyl-3h-bis[1]benzopyrano[3,4-b:6',5'-e]pyran-7(7ah)-one; (7aS,13aS)-9,10-Dimethoxy-3,3-dimethyl-13,13a-dihydro-3H-pyrano[2,3-c:6,5-f']dichromen-7(7aH)-one; (7aS,13aS)-9,10-dimethoxy-3,3-dimethyl-13,13a-dihydro-3H-pyrano[2,3-c:6,5-f']dichromen-7(7aH)-one.; SR-01000597503; CCRIS 8104; Deguelin/; (-)-Deguelin, Mundulea sericea; Spectrum_001044; Tocris-1770; Spectrum2_000298; Spectrum3_001122; Spectrum4_001965; Spectrum5_001852; SCHEMBL73183; BSPBio_002583; KBioGR_002434; KBioSS_001524; SPECTRUM201138; MLS006010295; SPBio_000236; CHEMBL393417; KBio2_001524; KBio2_004092; KBio2_006660; KBio3_002083; DTXSID10200231; HMS1923A05; HMS3268E12; 3H-Bis(1)benzopyrano(3,4-b:6',5'-e)pyran-7(7aH)-one, 13,13a-dihydro-9,10-dimethoxy-3,3-dimethyl-, (7aS-cis)-; EX-A4158; ZINC3978987; 1702AH; ABP000411; BDBM50505204; CCG-39856; LMPK12060019; s8132; AKOS024456769; ACN-053693; BCP9000596; CS-1802; SDCCGMLS-0066380.P001; NCGC00025288-01; NCGC00025288-02; NCGC00025288-03; (-)-Deguelin, >98% (HPLC), powder; AS-56004; HY-13425; SMR004701363; C10417; Q5251862; SR-01000597503-1; SR-01000597503-3; SR-01000597503-4; BRD-K61401890-001-02-0; BRD-K61401890-001-03-8; BRD-K61401890-001-04-6; (1S,14S)-17,18-dimethoxy-7,7-dimethyl-2,8,21-trioxapentacyclo[12.8.0.03,12.04,9.015,20]docosa-3(12),4(9),5,10,15,17,19-heptaen-13-one; (7aS,13aS)-9,10-Dimethoxy-3,3-dimethyl-13,13a-dihydro-3H,7aH-pyrano[2,3-c;6,5-f']dichromen-7-one; 13,13aS-Dihydro-9,10-dimethoxy-3,3-dimethyl-3H-[1]benzopyrano[3,4-b]pyrano[2,3-h][1]benzopyran-7(7aS)-one; 3H-[1]Benzopyrano[3,4-b]pyrano[2,3-h][1]benzopyran-7(7aH)-one, 13,13a-dihydro-9,10-dimethoxy-3,3-dimethyl-, (7aS,13aS)-; 3H-Bis(1)benzopyrano(3,4-b:6',5'-e)pyran-7(7aH)-one, 13,13a-dihydro-9,10-dimethoxy-3,3-dimethyl-, (7aS,13aS)-
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Species Origin Derris trifoliata ...     Click to Show/Hide
Derris trifoliata
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Fabales
Family: Fabaceae
Genus: Derris
Species: Derris trifoliata
Indigofera tinctoria
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Fabales
Family: Fabaceae
Genus: Indigofera
Species: Indigofera tinctoria
Disease Lung cancer [ICD-11: 2C25] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.728
 
MDCK Permeability
 -4.741
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 0.218
 
PPB
 97.3%
 
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
 6.928
 
T1/2
 2.482
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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Formula
C23H22O6
PubChem CID
107935
Canonical SMILES
CC1(C=CC2=C(O1)C=CC3=C2OC4COC5=CC(=C(C=C5C4C3=O)OC)OC)C
InChI
1S/C23H22O6/c1-23(2)8-7-12-15(29-23)6-5-13-21(24)20-14-9-17(25-3)18(26-4)10-16(14)27-11-19(20)28-22(12)13/h5-10,19-20H,11H2,1-4H3/t19-,20+/m1/s1
InChIKey
ORDAZKGHSNRHTD-UXHICEINSA-N
CAS Number
CAS 522-17-8
Herb ID
HBIN022961
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cisplatin      Bladder 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 BRCA1  Molecule Info 
Pathway MAP
                    In-vitro Model MGC-803 CVCL_5334 Gastric mucinous adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combined treatment of deguelin and cisplatin exhibited a marked inhibition of MGC-803 cell proliferation when compared with that of the single therapies in vitro.
          AG1478      Diabetic retinopathy     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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model HSC-4 CVCL_1289 Tongue squamous cell carcinoma Homo sapiens
Ca9-22 CVCL_1102 Gingival squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Deguelin Potentiates Apoptotic Activity of an EGFR Tyrosine Kinase Inhibitor (AG1478) in PIK3CA-Mutated Head and Neck Squamous Cell Carcinoma.
          Doxorubicin      Solid tumour/cancer     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 [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
                    In-vitro Model MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
HPDE CVCL_4376 Healthy Homo sapiens
                    Experimental
                    Result(s)		 Inhibition of autophagy by deguelin sensitizes pancreatic cancer cells to doxorubicin.
Target and Pathway
Target(s) Aurora kinase B (AURKB)  Molecule Info  [5]
Aurora kinase C (AURKC)  Molecule Info  [5]
Insulin-like growth factor I receptor (IGF1R)  Molecule Info  [6]
Phosphatase and tensin homolog (PTEN)  Molecule Info  [7]
Transcription factor p65 (RELA)  Molecule Info  [8]
KEGG Pathway Ras signaling pathway Click to Show/Hide
2 Rap1 signaling pathway
3 HIF-1 signaling pathway
4 FoxO signaling pathway
5 Oocyte meiosis
6 Endocytosis
7 PI3K-Akt signaling pathway
8 AMPK signaling pathway
9 Focal adhesion
10 Adherens junction
11 Signaling pathways regulating pluripotency of stem cells
12 Long-term depression
13 Ovarian steroidogenesis
14 Progesterone-mediated oocyte maturation
15 Pathways in cancer
16 Transcriptional misregulation in cancer
17 Proteoglycans in cancer
18 Glioma
19 Prostate cancer
20 Melanoma
Panther Pathway Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade Click to Show/Hide
2 Insulin/IGF pathway-protein kinase B signaling cascade
Pathway Interaction Database Plasma membrane estrogen receptor signaling Click to Show/Hide
2 SHP2 signaling
3 IGF1 pathway
4 Posttranslational regulation of adherens junction stability and dissassembly
5 Integrins in angiogenesis
6 Stabilization and expansion of the E-cadherin adherens junction
7 Aurora B signaling
8 Signaling by Aurora kinases
9 Aurora C signaling
10 FOXM1 transcription factor network
11 Aurora A signaling
Reactome IRS-related events triggered by IGF1R Click to Show/Hide
2 SHC-related events triggered by IGF1R
3 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
4 Separation of Sister Chromatids
5 Resolution of Sister Chromatid Cohesion
6 RHO GTPases Activate Formins
7 Mitotic Prometaphase
WikiPathways Senescence and Autophagy in Cancer Click to Show/Hide
2 Insulin Signaling
3 Endochondral Ossification
4 Focal Adhesion
5 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
6 Apoptosis
7 Signaling Pathways in Glioblastoma
8 TSH signaling pathway
9 MicroRNAs in cardiomyocyte hypertrophy
10 Mitotic Metaphase and Anaphase
11 Mitotic Prometaphase
12 Regulation of Microtubule Cytoskeleton
13 miR-targeted genes in lymphocytes - TarBase
14 miR-targeted genes in epithelium - TarBase
15 APC/C-mediated degradation of cell cycle proteins
16 EGF/EGFR Signaling Pathway
17 JAK/STAT
18 Gastric Cancer Network 1
19 Integrated Breast Cancer Pathway
References
Reference 1 Deguelin suppresses non-small cell lung cancer by inhibiting EGFR signaling and promoting GSK3Beta/FBW7-mediated Mcl-1 destabilization. Cell Death Dis. 2020 Feb 21;11(2):143.
Reference 2 Synergistic antitumor effects of combined deguelin and cisplatin treatment in gastric cancer cells. Oncol Lett. 2014 Oct;8(4):1603-1607.
Reference 3 Deguelin Potentiates Apoptotic Activity of an EGFR Tyrosine Kinase Inhibitor (AG1478) in PIK3CA-Mutated Head and Neck Squamous Cell Carcinoma. Int J Mol Sci. 2017 Jan 26;18(2):262.
Reference 4 Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin. Int J Mol Sci. 2017 Feb 10;18(2):370.
Reference 5 Deguelin, an Aurora B Kinase Inhibitor, Exhibits Potent Anti-Tumor Effect in Human Esophageal Squamous Cell Carcinoma. EBioMedicine. 2017 Dec;26:100-111.
Reference 6 A novel antitumor activity of deguelin targeting the insulin-like growth factor (IGF) receptor pathway via up-regulation of IGF-binding protein-3 expression in breast cancer. Cancer Lett. 2013 May 10;332(1):102-9.
Reference 7 Mitochondrial Complex I Inhibitors Expose a Vulnerability for Selective Killing of Pten-Null Cells. Cell Rep. 2018 Apr 3;23(1):58-67.
Reference 8 Deguelin suppresses pancreatic tumor growth and metastasis by inhibiting epithelial-to-mesenchymal transition in an orthotopic model. Oncogene. 2013 Aug 22;32(34):3980-91.
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