Natural Product (NP) Details

General Information of the NP (ID: NP4837)
Name
Costunolide
Synonyms
Costunolide; 553-21-9; (+)-costunolide; Costunlide; Costundide; Costunolid; Costus lactone; CHEMBL86416; CHEBI:3900; (3aS,6E,10E,11aR)-6,10-dimethyl-3-methylene-3a,4,5,8,9,11a-hexahydrocyclodeca[b]furan-2(3H)-one; (E,E)-6-alpha-Hydroxygermacra-1(10),4,11(13)-trien-12-oic acid gamma-lactone; (10S,1R)-3,7-dimethyl-11-methylene-13-oxabicyclo[8.3.0]trideca-2,6-dien-12-one; (E,E)-germacra-1(10),4,11(13)-trien-12-oic acid, 6-alpha-hydroxy-gamma-lactone; (3aS,6E,10E)-3-Methylene-6,10-dimethyl-2,3,3abeta,4,5,8,9,11aalpha-octahydrocyclodeca[b]furan-2-one; (3aS,6E,10E,11aR)-6,10-dimethyl-3-methylidene-3a,4,5,8,9,11a-hexahydrocyclodeca[b]furan-2(3H)-one; melampolide; NSC106404; Costunolide,(S); PubChem6258; SCHEMBL92714; Costunolide, >=97% (HPLC); HMS3269I17; HMS3413B19; HMS3677B19; HY-N0036; BDBM50411242; MFCD00210262; ZINC30726859; AKOS015840065; AKOS015969714; CS-1487; MCULE-2058016705; NCGC00381718-02; (3aS,6E,10E,11aR)-6,10-dimethyl-3-methylidene-3a,4,5,8,9,11a-hexahydrocyclodeca[b]furan-2-one; AC-28334; AS-17708; V1471; C09382; 553C219; Q5175227; BRD-K26833429-001-01-0; (3aS,6E,10E,11aR)-3a,4,5,8,9,11a-Hexahydro-6,10-dimethyl-3-methylene-cyclodeca[b]furan-2(3H)-one; (3aS,6E,10E,11aR)-6,10-dimethyl-3-methylene-3,3a,4,5,8,9-hexahydrocyclodeca[b]furan-2(11aH)-one; (3aS,6E,10E,11aR)-6,10-dimethyl-3-methylene-3a,4,5,8,9,11a-hexahydrocyclodeca[b]furan-2-one; Cyclodeca[b]furan-2(3H)-one, 3a,4,5,8,9,11a-hexahydro-6,10-dimethyl-3-methylene-, (3aS,6E,10E,11aR)-; NCGC00381718-02_C15H20O2_Cyclodeca[b]furan-2(3H)-one, 3a,4,5,8,9,11a-hexahydro-6,10-dimethyl-3-methylene-, (3aS,6E,10E,11aR)-
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Species Origin Magnolia sieboldii ...     Click to Show/Hide
Magnolia sieboldii
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Magnoliales
Family: Magnoliaceae
Genus: Magnolia
Species: Magnolia sieboldii
Disease Stomach cancer [ICD-11: 2B72] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.774
 
MDCK Permeability
 -4.616
 
PAMPA
 - - -
 
HIA
 - -
 
Distribution
VDss
 0.098
 
PPB
 96%
 
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
 9.487
 
T1/2
 1.836
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
C15H20O2
PubChem CID
5281437
Canonical SMILES
CC1=CCCC(=CC2C(CC1)C(=C)C(=O)O2)C
InChI
1S/C15H20O2/c1-10-5-4-6-11(2)9-14-13(8-7-10)12(3)15(16)17-14/h5,9,13-14H,3-4,6-8H2,1-2H3/b10-5+,11-9+/t13-,14+/m0/s1
InChIKey
HRYLQFBHBWLLLL-AHNJNIBGSA-N
CAS Number
CAS 553-21-9
ChEBI ID
CHEBI:3900
Herb ID
HBIN021599
SymMap ID
SMIT11810
TCMSP ID
MOL010825
TTD Drug ID
D07KNG
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Imatinib      Mantle cell lymphoma     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		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Costunolide promotes imatinib-induced apoptosis in chronic myeloid leukemia cells via the Bcr/Abl-Stat5 pathway.
          Ionizing radiation      Renal Insufficiency     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		 Up-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation CDK1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation MPIP3  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation RAD53  Molecule Info 
Pathway MAP
                    In-vitro Model HA22T/VGH CVCL_7046 Adult hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells.
          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 [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation PIK3CB  Molecule Info 
Pathway MAP
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Costunolide enhances sensitivity of K562/ADR chronic myeloid leukemia cells to doxorubicin through PI3K/Akt pathway.
Target and Pathway
Target(s) Microtubule-associated protein (MAP)  Molecule Info  [5]
References
Reference 1 Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells. BMC Complement Altern Med. 2019 Jun 26;19(1):151.
Reference 2 Costunolide promotes imatinib-induced apoptosis in chronic myeloid leukemia cells via the Bcr/Abl-Stat5 pathway. Phytother Res. 2018 Sep;32(9):1764-1769.
Reference 3 Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells. Radiat Oncol. 2011 May 30;6:56.
Reference 4 Costunolide enhances sensitivity of K562/ADR chronic myeloid leukemia cells to doxorubicin through PI3K/Akt pathway. Phytother Res. 2019 Jun;33(6):1683-1688.
Reference 5 A sesquiterpene lactone, costunolide, interacts with microtubule protein and inhibits the growth of MCF-7 cells. Chem Biol Interact. 2004 Jan 15;147(1):79-86.
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