Natural Product (NP) Details

General Information of the NP (ID: NP8057)
Name
Parthenolide
Synonyms
parthenolide; 20554-84-1; (-)-Parthenolide; MFCD00134592; CHEBI:7939; 4,5-alpha-Epoxy-6-beta-hydroxygermacra-1(10),11(13)-dien-12-oic acid gamma-lactone; (1aR,4E,7aS,10aS,10bR)-1a,5-dimethyl-8-methylidene-2,3,6,7,7a,8,10a,10b-octahydrooxireno[9,10]cyclodeca[1,2-b]furan-9(1aH)-one; (3aS,9aR,10aR,10bS,E)-6,9a-dimethyl-3-methylene-3a,4,5,8,9,9a,10a,10b-octahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-2(3H)-one; 29552-41-8; partenolide; Parthenolide, Tanacetum parthenium; Prestwick2_000550; Prestwick3_000550; Epitope ID:115014; SCHEMBL8220; BSPBio_000599; BSPBio_001308; MLS002153872; BPBio1_000659; CHEMBL465158; parthenolide-(alternate-stereo); SCHEMBL13367522; BCBcMAP01_000041; Parthenolide, >=98% (HPLC); HMS1361B10; HMS1569N21; HMS1791B10; HMS1989B10; HMS2096N21; HMS3402B10; HMS3713N21; BCP10404; HY-N0141; ZINC4492886; AKOS016010226; CCG-208244; CS-1919; IDI1_033778; NCGC00163415-01; NCGC00163415-04; AS-17479; SMR001233226; AB0019832; AB00513860; V0355; X-1866; 552P418; Q-100253; (-)-Parthenolide; NSC-157035; NSC 157035; NSC157035; Parthenolide, United States Pharmacopeia (USP) Reference Standard; (1S,2R,4R,7E,11S)-4,8-dimethyl-12-methylidene-3,14-dioxatricyclo[9.3.0.02,4]tetradec-7-en-13-one; (3aS,10R,11R,11aS,6E)-3-Methylene-6,10-dimethyl-10,11-epoxy-1-oxa-2,3,3a,4,5,8,9,10,11,11a-decahydro-1H-cyclopentacyclodecene-2-one
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Species Origin Tanacetum parthenium ...     Click to Show/Hide
Tanacetum parthenium
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Asterales
Family: Asteraceae
Genus: Tanacetum
Species: Tanacetum parthenium
Disease Lung cancer [ICD-11: 2C25] Investigative [1]
Structure
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2D MOL

3D MOL

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Formula
C15H20O3
PubChem CID
7251185
Canonical SMILES
CC1=CCCC2(C(O2)C3C(CC1)C(=C)C(=O)O3)C
InChI
1S/C15H20O3/c1-9-5-4-8-15(3)13(18-15)12-11(7-6-9)10(2)14(16)17-12/h5,11-13H,2,4,6-8H2,1,3H3/b9-5+/t11-,12-,13+,15+/m0/s1
InChIKey
KTEXNACQROZXEV-PVLRGYAZSA-N
CAS Number
CAS 20554-84-1
ChEBI ID
CHEBI:7939
Herb ID
HBIN038876
SymMap ID
SMIT17112
TTD Drug ID
D0M4KE
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Balsalazide      Indeterminate colitis     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
Up-regulation Activity p105  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    In-vivo Model Sixty specific pathogen-free mice (Balb/C female mice, 6 week) were used in this study.
                    Experimental
                    Result(s)		 Parthenolide potentiates the efficacy of balsalazide through synergistic inhibition of NF-KappaB activation and the combination of dual agents prevents colon carcinogenesis from chronic inflammation.
    β. A List of Drug(s) Whose Adverse Effect can be Decreased by This NP
          Epirubicin      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Decreasing Adverse Drug Reaction     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 BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Parthenolide along with Epirubicin chemotherapy drug could improve cytotoxicity and apoptosis and reduces IC50.
Target and Pathway
Target(s) I-kappa-B-kinase beta (IKKB)  Molecule Info  [4]
Nuclear factor NF-kappa-B (NFKB)  Molecule Info  [5]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 Ras signaling pathway
3 Chemokine signaling pathway
4 NF-kappa B signaling pathway
5 FoxO signaling pathway
6 mTOR signaling pathway
7 PI3K-Akt signaling pathway
8 Apoptosis
9 Osteoclast differentiation
10 Toll-like receptor signaling pathway
11 NOD-like receptor signaling pathway
12 RIG-I-like receptor signaling pathway
13 Cytosolic DNA-sensing pathway
14 T cell receptor signaling pathway
15 B cell receptor signaling pathway
16 TNF signaling pathway
17 Neurotrophin signaling pathway
18 Insulin signaling pathway
19 Adipocytokine signaling pathway
20 Type II diabetes mellitus
21 Non-alcoholic fatty liver disease (NAFLD)
22 Epithelial cell signaling in Helicobacter pylori infection
23 Shigellosis
24 Chagas disease (American trypanosomiasis)
25 Toxoplasmosis
26 Hepatitis C
27 Hepatitis B
28 Influenza A
29 HTLV-I infection
30 Herpes simplex infection
31 Epstein-Barr virus infection
32 Pathways in cancer
33 MicroRNAs in cancer
34 Pancreatic cancer
35 Prostate cancer
36 Chronic myeloid leukemia
37 Acute myeloid leukemia
38 Small cell lung cancer
39 Legionellosis
40 Viral carcinogenesis
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
Panther Pathway Apoptosis signaling pathway Click to Show/Hide
2 B cell activation
3 Inflammation mediated by chemokine and cytokine signaling pathway
4 Interleukin signaling pathway
5 PDGF signaling pathway
6 T cell activation
7 Toll receptor signaling pathway
Pathwhiz Pathway Intracellular Signalling Through Adenosine Receptor A2a and Adenosine Click to Show/Hide
2 Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Pathway Interaction Database Fc-epsilon receptor I signaling in mast cells Click to Show/Hide
2 BCR signaling pathway
3 GMCSF-mediated signaling events
4 Atypical NF-kappaB pathway
5 TCR signaling in na&#xef
6
7 Canonical NF-kappaB pathway
8 TRAIL signaling pathway
9 TCR signaling in na&#xef
10
11 FAS (CD95) signaling pathway
12 IL1-mediated signaling events
13 mTOR signaling pathway
14 TNF receptor signaling pathway
15 FoxO family signaling
16 p75(NTR)-mediated signaling
17 Validated transcriptional targets of TAp63 isoforms
18 Endogenous TLR signaling
19 IL12-mediated signaling events
20 Alternative NF-kappaB pathway
Reactome Activation of NF-kappaB in B cells Click to Show/Hide
2 NOD1/2 Signaling Pathway
3 RIP-mediated NFkB activation via ZBP1
4 p75NTR recruits signalling complexes
5 NF-kB is activated and signals survival
6 FCERI mediated NF-kB activation
7 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
8 Interleukin-1 signaling
9 Regulation of TNFR1 signaling
10 TNFR1-induced NFkappaB signaling pathway
11 IKBKB deficiency causes SCID
12 IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)
13 IkBA variant leads to EDA-ID
14 CLEC7A (Dectin-1) signaling
15 MAP3K8 (TPL2)-dependent MAPK1/3 activation
16 TRAF6 mediated NF-kB activation
17 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
18 IRAK1 recruits IKK complex
19 IKK complex recruitment mediated by RIP1
20 IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation
21 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
22 Interleukin-1 processing
23 Dectin-1 mediated noncanonical NF-kB signaling
24 NIK-->noncanonical NF-kB signaling
WikiPathways Toll-like receptor signaling pathway Click to Show/Hide
2 Estrogen signaling pathway
3 TCR Signaling Pathway
4 Insulin Signaling
5 IL-4 Signaling Pathway
6 MAPK Signaling Pathway
7 NLR Proteins
8 Hair Follicle Development: Induction (Part 1 of 3)
9 MyD88 cascade initiated on plasma membrane
10 Cardiac Hypertrophic Response
11 Cytosolic sensors of pathogen-associated DNA
12 MyD88 dependent cascade initiated on endosome
13 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
14 MyD88:Mal cascade initiated on plasma membrane
15 Fc epsilon receptor (FCERI) signaling
16 MyD88-independent cascade
17 Signaling by the B Cell Receptor (BCR)
18 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
19 Structural Pathway of Interleukin 1 (IL-1)
20 EBV LMP1 signaling
21 Polycystic Kidney Disease Pathway
22 Apoptosis
23 Quercetin and Nf-kB/ AP-1 Induced Cell Apoptosis
24 BDNF signaling pathway
25 Interleukin-11 Signaling Pathway
26 AGE/RAGE pathway
27 TNF alpha Signaling Pathway
28 B Cell Receptor Signaling Pathway
29 IL17 signaling pathway
30 TWEAK Signaling Pathway
31 Leptin signaling pathway
32 RANKL/RANK Signaling Pathway
33 Signalling by NGF
34 IL-1 signaling pathway
35 TCR signaling
36 RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
37 Interleukin-1 signaling
38 Apoptosis Modulation and Signaling
39 Type II diabetes mellitus
40 MicroRNAs in cardiomyocyte hypertrophy
41 Regulation of toll-like receptor signaling pathway
42 Osteopontin Signaling
43 NOD pathway
44 DNA Damage Response (only ATM dependent)
45 SIDS Susceptibility Pathways
46 Nuclear Receptors Meta-Pathway
47 TSLP Signaling Pathway
48 Neural Crest Differentiation
49 Interleukin-1 processing
50 Folate Metabolism
51 Vitamin B12 Metabolism
52 Selenium Micronutrient Network
References
Reference 1 Parthenolide inhibits the growth of non-small cell lung cancer by targeting epidermal growth factor receptor. Cancer Cell Int. 2020 Nov 23;20(1):561.
Reference 2 Combined Parthenolide and Balsalazide Have Enhanced Antitumor Efficacy Through Blockade of NF-KappaB Activation. Mol Cancer Res. 2017 Feb;15(2):141-151.
Reference 3 Anticancer and apoptotic activities of parthenolide in combination with epirubicin in mda-mb-468 breast cancer cells. Mol Biol Rep. 2020 Aug;47(8):5807-5815.
Reference 4 The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 2001 Aug;8(8):759-66.
Reference 5 Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J Exp Med. 2005 Jan 3;201(1):105-15.
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