Natural Product (NP) Details

General Information of the NP (ID: NP0703)
Name
Cucurbitacin E
Synonyms
Cucurbitacin E; 18444-66-1; alpha-Elaterin; alpha-Elaterine; ELATERIN, ALPHA; UNII-V8A45XYI21; CHEBI:3944; V8A45XYI21; [(E,6R)-6-[(8S,9R,10R,13R,14S,16R,17R)-2,16-dihydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-8,10,12,15,16,17-hexahydro-7H-cyclopenta[a]phenanthren-17-yl]-6-hydroxy-2-methyl-5-oxohept-3-en-2-yl] acetate; 19-Norlanosta-1,5,23-triene-3,11,22-trione,25-(acetyloxy)-2,16,20-trihydroxy-9-methyl-, (9b,10a,16a,23E)-; Cucurbitacine E; .alpha.-Elaterin; .alpha.-Elaterine; Cucurbitacine-E; CUE; NSC 106399; Cucurbitacin-E; NSC106399; 19-Nor-9.beta.,5,23-triene-3,11,22-trione, 2,16.alpha.,20,25-tetrahydroxy-9-methyl-, 25-acetate; 19-Norlanosta-1,23-triene-3,11,22-trione, 25-(acetyloxy)-2,16,20-trihydroxy-9-methyl-, (9.beta.,10.alpha.,16.alpha.,23E)-; C32H44O8; EINECS 242-325-2; NSC-106399; BRN 2343323; cucurbitacin E derivatives; SCHEMBL140616; (R,E)-6-((8S,9R,10R,13R,14S,16R,17R)-2,16-dihydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-4,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl)-6-hydroxy-2-methyl-5-oxohept-3-en-2-yl acetate; HY-N0417; ZINC4097800; LMST01010107; MFCD00135936; NSC521775; AKOS015896851; CS-3817; NSC-521775; 19-Norlanosta-1,5,23-triene-3,11,22-trione, 25-(acetyloxy)-2,16,20-trihydroxy-9-methyl-, (9beta,10alpha,16alpha,23E)-; 2,16alpha,20,25-Tetrahydroxy-9beta-methyl-10alpha,-19-norlanosta-1,5,23(E)-triene-3,11,22-trione 25-acetate; 25-(Acetyloxy)-2,16,20-trihydroxy-9-methyl-19-norlanosta-1,5,23-triene-3,11,22-trione (9beta,10alpha,16alpha,23E)-; N2791; Y0059; C08797; 444C661; Q5192451; UNII-W3RWP6CB48 component NDYMQXYDSVBNLL-MUYMLXPFSA-N; (23E)-25-acetyloxy-2,16alpha,20-trihydroxy-9beta-methyl-19-nor-10alpha-lanosta-1,5,23-triene-3,11,22-trione; (4R,23E)-2,16alpha,20-trihydroxy-9beta,10,14-trimethyl-1,11,22-trioxo-4,9-cyclo-9,10-secocholesta-2,5,23-trien-25-yl acetate; 19-Nor-9-beta,10-alpha-lanosta-1,5,23-triene-3,11,22-trione, 2,16-alpha,20,25-tetrahydroxy-9-methyl-, 25-acetate; 19-Nor-9beta,10alpha-lanosta-1,5,23-triene-3,11,22-trione, 2,16alpha,20,25-tetrahydroxy-9-methyl-, 25-acetate (8CI); 2,16alpha,20,25-tetrahydroxy-9-methyl-19-nor-9beta,10alpha-lanosta-1,5,23-triene-3,11,22-trione 25-acetate
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Species Origin Cucumic melo ...     Click to Show/Hide
Cucumic melo
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Cucurbitales
Family: Cucurbitaceae
Genus: Cucumis
Species: Cucumic melo
Disease Esophageal cancer [ICD-11: 2B70] Investigative [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.932
 
MDCK Permeability
 -4.582
 
PAMPA
 +++
 
HIA
 - - -
 
Distribution
VDss
 0.072
 
PPB
 88.3%
 
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
 2.2
 
T1/2
 1.462
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
C32H44O8
PubChem CID
5281319
Canonical SMILES
CC(=O)OC(C)(C)C=CC(=O)C(C)(C1C(CC2(C1(CC(=O)C3(C2CC=C4C3C=C(C(=O)C4(C)C)O)C)C)C)O)O
InChI
1S/C32H44O8/c1-17(33)40-27(2,3)13-12-23(36)32(9,39)25-21(35)15-29(6)22-11-10-18-19(14-20(34)26(38)28(18,4)5)31(22,8)24(37)16-30(25,29)7/h10,12-14,19,21-22,25,34-35,39H,11,15-16H2,1-9H3/b13-12+/t19-,21-,22+,25+,29+,30-,31+,32+/m1/s1
InChIKey
NDYMQXYDSVBNLL-MUYMLXPFSA-N
CAS Number
CAS 18444-66-1
ChEBI ID
CHEBI:3944
Herb ID
HBIN021850
SymMap ID
SMIT01356
TCMSP ID
MOL002444
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          5-fluorouracil      Solid tumour/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 ABCC1  Molecule Info 
Pathway MAP
                    In-vitro Model DLD-1 CVCL_0248 Colon adenocarcinoma Homo sapiens
HCT 8 CVCL_2478 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
FHC CVCL_3688 Healthy Homo sapiens
                    In-vivo Model Six-week-old female nude mice received a subcutaneous injection of HCT-8/FU cells (1 * 106 suspended in 100 uL of PBS) on the right flank.
                    Experimental
                    Result(s)		 Cucurbitacin E chemosensitizes colorectal cancer cells via mitigating TFAP4/Wnt/Beta-Catenin signaling.
          Doxorubicin      Solid tumour/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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model NCI-N87 CVCL_1603 Gastric tubular adenocarcinoma Homo sapiens
BGC-823 CVCL_3360 Gastric cancer Homo sapiens
SNU-16 CVCL_0076 Gastric adenocarcinoma Homo sapiens
SGC-7901 CVCL_0520 Human gastric cancer Homo sapiens
MGC-803 CVCL_5334 Gastric mucinous adenocarcinoma Homo sapiens
                    In-vivo Model Female BALB/c nude mice (4-5 weeks old) were subcutaneously injected with 1*107 NCI-N87 cells (suspended in 100 ul of PBS with 50% Matrigel) to establish tumors.
                    Experimental
                    Result(s)		 Cucurbitacin E inhibits cellular proliferation and enhances the chemo-response in gastric cancer by suppressing AKt activation.
Target and Pathway
Target(s) Cytochrome c (GADD45G)  Molecule Info  [4]
DNA damage-inducible transcript 1 (GADD45A)  Molecule Info  [5]
Negative growth-regulatory protein MyD118 (GADD45B)  Molecule Info  [5]
References
Reference 1 Cucurbitacin E inhibits esophageal carcinoma cell proliferation, migration, and invasion by suppressing Rac1 expression through PI3K/AKT/mTOR pathway. Anticancer Drugs. 2020 Sep;31(8):847-855.
Reference 2 Cucurbitacin E Chemosensitizes Colorectal Cancer Cells via Mitigating TFAP4/Wnt/Beta-Catenin Signaling. J Agric Food Chem. 2020 Nov 18.
Reference 3 Cucurbitacin E inhibits cellular proliferation and enhances the chemo-response in gastric cancer by suppressing AKt activation. J Cancer. 2019 Oct 6;10(23):5843-5851.
Reference 4 Therapeutic ROS targeting of GADD45Gamma in the induction of G2/M arrest in primary human colorectal cancer cell lines by cucurbitacin E. Cell Death Dis. 2014 Apr 24;5(4):e1198.
Reference 5 Inducement of mitosis delay by cucurbitacin E, a novel tetracyclic triterpene from climbing stem of Cucumis melo L., through GADD45Gamma in human brain malignant glioma (GBM) 8401 cells. Cell Death Dis. 2014 Feb 27;5(2):e1087.
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