Natural Product (NP) Details

General Information of the NP (ID: NP9343)
Name
Cucurbitacin D
Synonyms
Cucurbitacin D; Elatericin A; Cucurbitacine (D); 3877-86-9; Elatericine A; UNII-5I62H4ORC7; 5I62H4ORC7; CHEBI:3943; NSC308606; (2S,8S,9R,10R,13R,14S,16R,17R)-17-[(E,2R)-2,6-dihydroxy-6-methyl-3-oxohept-4-en-2-yl]-2,16-dihydroxy-4,4,9,13,14-pentamethyl-2,7,8,10,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthrene-3,11-dione; NSC 308606; NSC 521776; 19-nor-9.beta.,23-diene-3,11,22-trione, 9-methyl-2.beta.,16.alpha.,20,25-tetrahydroxy-; 19-Norlanosta-5,11,22-trione, 2,16,20,25-tetrahydroxy-9-methyl-, (2.beta.,9.beta.,10.alpha.,16.alpha.,23E)-; cucurbitacin D derivatives; 19-Norlanosta-5,23-diene-3,11,22-trione,2,16,20,25-tetrahydroxy-9-methyl-, (2b,9b,10a,16a,23E)-; SCHEMBL230654; CHEMBL493646; HY-N1986; ZINC4097799; LMST01010106; NSC521776; AKOS015896755; MCULE-5684742998; NSC-308606; NSC-521776; NCGC00385253-01; 19-Nor-9-beta,10-alpha-lanosta-5,23-diene-3,11,22-trione, 9-methyl-2-beta,16-alpha,20,25-tetrahydroxy-; CS-0018307; C08796; Q15410915; UNII-W3RWP6CB48 component SRPHMISUTWFFKJ-QJNWWGCFSA-N; (23E)-2beta,16alpha,20,25-tetrahydroxy-10alpha-cucurbita-5,23-diene-3,11,22-trione; (23E)-2beta,16alpha,20,25- tetrahydroxy-9beta-methyl-19-nor-10alpha-lanosta-5,23-diene-3,11,22-trione; (2S,4R,23E)-2,16,20,25-tetrahydroxy-9beta,10,14-trimethyl-4,9-cyclo-9,10-seco-16alpha-cholesta-5,23-diene-1,11,22-trione; 19-Norlanosta-5,23-diene-3,11,22-trione, 2,16,20,25-tetrahydroxy-9-methyl-, (2beta,9beta,10alpha,16alpha,23E)- (9CI); NCGC00385253-01_C30H44O7_(2S,4R,9beta,16alpha,23E)-2,16,20,25-Tetrahydroxy-9,10,14-trimethyl-4,9-cyclo-9,10-secocholesta-5,23-diene-1,11,22-trione
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Species Origin Cucurbitaceae ...     Click to Show/Hide
Cucurbitaceae
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Cucurbitales
Family: Cucurbitaceae
Disease Cervical cancer [ICD-11: 2C77] Investigative [1]
Structure
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2D MOL

3D MOL

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Formula
C30H44O7
PubChem CID
5281318
Canonical SMILES
CC1(C2=CCC3C4(CC(C(C4(CC(=O)C3(C2CC(C1=O)O)C)C)C(C)(C(=O)C=CC(C)(C)O)O)O)C)C
InChI
1S/C30H44O7/c1-25(2,36)12-11-21(33)30(8,37)23-19(32)14-27(5)20-10-9-16-17(13-18(31)24(35)26(16,3)4)29(20,7)22(34)15-28(23,27)6/h9,11-12,17-20,23,31-32,36-37H,10,13-15H2,1-8H3/b12-11+/t17-,18+,19-,20+,23+,27+,28-,29+,30+/m1/s1
InChIKey
SRPHMISUTWFFKJ-QJNWWGCFSA-N
CAS Number
CAS 3877-86-9
ChEBI ID
CHEBI:3943
Herb ID
HBIN021848
SymMap ID
SMIT04680
TCMSP ID
MOL002447
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Adverse Effect can be Decreased by This NP
          Gefitinib      Lung 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 [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
                    In-vitro Model HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Cucurbitacin D overcomes gefitinib resistance by blocking EGF binding to EGFR and inducing cell death in NSCLCs.
Target and Pathway
Target(s) Apoptosis regulator Bcl-2 (BCL-2)  Molecule Info  [3]
Apoptosis regulator Bcl-xL (BCL-xL)  Molecule Info  [3]
DNA-binding factor KBF1 (p105)  Molecule Info  [3]
HepG2 glucose transporter (SLC2A1)  Molecule Info  [4]
Proliferating cell nuclear antigen (PCNA)  Molecule Info  [4]
Ribonucleoside-diphosphate reductase M1 (RRM1)  Molecule Info  [5]
Ribonucleoside-diphosphate reductase M2 (RRM2)  Molecule Info  [5]
BioCyc Pyrimidine deoxyribonucleotides biosynthesis from CTP Click to Show/Hide
2 Pyrimidine deoxyribonucleotides de novo biosynthesis
3 Guanosine nucleotides de novo biosynthesis
4 Superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis
5 Superpathway of purine nucleotide salvage
6 Purine nucleotides de novo biosynthesis
7 Adenosine deoxyribonucleotides de novo biosynthesis
8 Guanosine deoxyribonucleotides de novo biosynthesis
KEGG Pathway Purine metabolism Click to Show/Hide
2 Pyrimidine metabolism
3 Glutathione metabolism
4 Metabolic pathways
5 DNA replication
6 Base excision repair
7 Nucleotide excision repair
8 Mismatch repair
9 Cell cycle
10 Hepatitis B
11 HTLV-I infection
12 Ras signaling pathway
13 NF-kappa B signaling pathway
14 PI3K-Akt signaling pathway
15 Apoptosis
16 Jak-STAT signaling pathway
17 Amyotrophic lateral sclerosis (ALS)
18 Toxoplasmosis
19 Pathways in cancer
20 Transcriptional misregulation in cancer
21 Pancreatic cancer
22 Chronic myeloid leukemia
23 Small cell lung cancer
24 HIF-1 signaling pathway
25 Sphingolipid signaling pathway
26 Protein processing in endoplasmic reticulum
27 Adrenergic signaling in cardiomyocytes
28 Focal adhesion
29 Neurotrophin signaling pathway
30 Cholinergic synapse
31 Tuberculosis
32 Epstein-Barr virus infection
33 MicroRNAs in cancer
34 Colorectal cancer
35 Prostate cancer
36 p53 signaling pathway
37 MAPK signaling pathway
38 cAMP signaling pathway
39 Chemokine signaling pathway
40 Osteoclast differentiation
41 Toll-like receptor signaling pathway
42 NOD-like receptor signaling pathway
43 RIG-I-like receptor signaling pathway
44 Cytosolic DNA-sensing pathway
45 T cell receptor signaling pathway
46 B cell receptor signaling pathway
47 TNF signaling pathway
48 Prolactin signaling pathway
49 Adipocytokine signaling pathway
50 Non-alcoholic fatty liver disease (NAFLD)
51 Cocaine addiction
52 Epithelial cell signaling in Helicobacter pylori infection
53 Shigellosis
54 Salmonella infection
55 Pertussis
56 Legionellosis
57 Leishmaniasis
58 Chagas disease (American trypanosomiasis)
59 Amoebiasis
60 Hepatitis C
61 Measles
62 Influenza A
63 Herpes simplex infection
64 Viral carcinogenesis
65 Acute myeloid leukemia
66 Inflammatory bowel disease (IBD)
NetPath Pathway IL2 Signaling Pathway Click to Show/Hide
2 TGF_beta_Receptor Signaling Pathway
3 Notch Signaling Pathway
4 IL5 Signaling Pathway
5 TCR Signaling Pathway
6 IL3 Signaling Pathway
7 Leptin Signaling Pathway
8 RANKL Signaling Pathway
9 TSLP Signaling Pathway
10 EGFR1 Signaling Pathway
11 IL1 Signaling Pathway
12 TNFalpha Signaling Pathway
Panther Pathway De novo purine biosynthesis Click to Show/Hide
2 De novo pyrimidine deoxyribonucleotide biosynthesis
3 DNA replication
4 Apoptosis signaling pathway
5 CCKR signaling map ST
6 Oxidative stress response
7 p53 pathway
8 T cell activation
Pathwhiz Pathway Purine Metabolism Click to Show/Hide
2 Nucleotide Excision Repair
3 Pyrimidine Metabolism
4 Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
5 Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Pathway Interaction Database E2F transcription factor network Click to Show/Hide
2 Direct p53 effectors
3 Validated nuclear estrogen receptor alpha network
4 BARD1 signaling events
5 IL2 signaling events mediated by PI3K
6 IL3-mediated signaling events
7 Caspase Cascade in Apoptosis
8 EPO signaling pathway
9 IL2 signaling events mediated by STAT5
10 Role of Calcineurin-dependent NFAT signaling in lymphocytes
11 IL2-mediated signaling events
12 Ceramide signaling pathway
13 RXR and RAR heterodimerization with other nuclear receptor
14 ATF-2 transcription factor network
15 C-MYB transcription factor network
16 HIV-1 Nef: Negative effector of Fas and TNF-alpha
17 Signaling events mediated by Stem cell factor receptor (c-Kit)
18 Validated targets of C-MYC transcriptional repression
19 Fc-epsilon receptor I signaling in mast cells
20 BCR signaling pathway
21 LPA receptor mediated events
22 Atypical NF-kappaB pathway
23 Canonical NF-kappaB pathway
24 CD40/CD40L signaling
25 IL12-mediated signaling events
26 Alternative NF-kappaB pathway
27 Osteopontin-mediated events
28 Angiopoietin receptor Tie2-mediated signaling
29 Signaling events mediated by HDAC Class I
30 Regulation of Telomerase
31 IL1-mediated signaling events
32 Glucocorticoid receptor regulatory network
33 TNF receptor signaling pathway
34 amb2 Integrin signaling
35 IL23-mediated signaling events
Reactome E2F mediated regulation of DNA replication Click to Show/Hide
2 G0 and Early G1
3 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
4 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
5 HDR through Homologous Recombination (HRR)
6 Dual Incision in GG-NER
7 Dual incision in TC-NER
8 Gap-filling DNA repair synthesis and ligation in TC-NER
9 G1/S-Specific Transcription
10 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
11 The NLRP1 inflammasome
12 Activation of BAD and translocation to mitochondria
13 Activation of NF-kappaB in B cells
14 RIP-mediated NFkB activation via ZBP1
15 Regulated proteolysis of p75NTR
16 NF-kB is activated and signals survival
17 Senescence-Associated Secretory Phenotype (SASP)
18 FCERI mediated NF-kB activation
19 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
20 Transcriptional regulation of white adipocyte differentiation
21 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
22 Interleukin-1 processing
23 IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)
24 IkBA variant leads to EDA-ID
25 CLEC7A (Dectin-1) signaling
26 CD209 (DC-SIGN) signaling
27 CLEC7A/inflammasome pathway
28 MAP3K8 (TPL2)-dependent MAPK1/3 activation
29 TRAF6 mediated NF-kB activation
WikiPathways Nucleotide Metabolism Click to Show/Hide
2 Retinoblastoma (RB) in Cancer
3 Integrated Pancreatic Cancer Pathway
4 Metabolism of nucleotides
5 Fluoropyrimidine Activity
6 Senescence and Autophagy in Cancer
7 Mismatch repair
8 DNA Replication
9 G1 to S cell cycle control
10 EGF/EGFR Signaling Pathway
11 S Phase
12 Nifedipine Activity
13 Primary Focal Segmental Glomerulosclerosis FSGS
14 Nucleotide Excision Repair
15 Telomere Maintenance
16 Synthesis of DNA
17 Mitotic G1-G1/S phases
18 Cell Cycle
19 Base Excision Repair
20 IL-6 signaling pathway
21 IL-3 Signaling Pathway
22 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
23 Apoptosis
24 Amyotrophic lateral sclerosis (ALS)
25 TNF alpha Signaling Pathway
26 IL-7 Signaling Pathway
27 Leptin signaling pathway
28 Intrinsic Pathway for Apoptosis
29 Apoptosis Modulation and Signaling
30 DNA Damage Response (only ATM dependent)
31 IL-2 Signaling Pathway
32 FAS pathway and Stress induction of HSP regulation
33 Focal Adhesion
34 Kit receptor signaling pathway
35 Nanoparticle triggered autophagic cell death
36 Corticotropin-releasing hormone
37 Interleukin-11 Signaling Pathway
38 Prostate Cancer
39 miR-targeted genes in muscle cell - TarBase
40 miR-targeted genes in lymphocytes - TarBase
41 miR-targeted genes in leukocytes - TarBase
42 Integrated Breast Cancer Pathway
43 Integrated Cancer pathway
44 TP53 Network
45 Influenza A virus infection
46 IL-5 Signaling Pathway
47 Toll-like receptor signaling pathway
48 SIDS Susceptibility Pathways
49 TCR Signaling Pathway
50 Notch Signaling Pathway
51 TGF Beta Signaling Pathway
52 Oxidative Stress
53 IL-4 Signaling Pathway
54 Apoptosis Modulation by HSP70
55 MAPK Signaling Pathway
56 Myometrial Relaxation and Contraction Pathways
57 IL1 and megakaryotyces in obesity
58 Apoptosis-related network due to altered Notch3 in ovarian cancer
59 Hair Follicle Development: Cytodifferentiation (Part 3 of 3)
60 Hair Follicle Development: Organogenesis (Part 2 of 3)
61 Hair Follicle Development: Induction (Part 1 of 3)
62 Selenium Metabolism and Selenoproteins
63 Cardiac Hypertrophic Response
64 Cytosolic sensors of pathogen-associated DNA
65 Fc epsilon receptor (FCERI) signaling
66 Transcriptional Regulation of White Adipocyte Differentiation
67 Signaling by the B Cell Receptor (BCR)
68 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
69 Structural Pathway of Interleukin 1 (IL-1)
70 EBV LMP1 signaling
71 Aryl Hydrocarbon Receptor
72 T-Cell Receptor and Co-stimulatory Signaling
73 Quercetin and Nf-kB/ AP-1 Induced Cell Apoptosis
74 BDNF signaling pathway
75 Oncostatin M Signaling Pathway
76 AGE/RAGE pathway
77 B Cell Receptor Signaling Pathway
78 TSLP Signaling Pathway
79 IL17 signaling pathway
80 Neural Crest Differentiation
81 TWEAK Signaling Pathway
82 RANKL/RANK Signaling Pathway
83 Signalling by NGF
84 IL-1 signaling pathway
85 TCR signaling
86 RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
87 Interleukin-1 signaling
88 Interleukin-1 processing
89 Folate Metabolism
90 TFs Regulate miRNAs related to cardiac hypertrophy
91 MicroRNAs in cardiomyocyte hypertrophy
92 Vitamin B12 Metabolism
93 Selenium Micronutrient Network
94 Regulation of toll-like receptor signaling pathway
95 Osteopontin Signaling
References
Reference 1 Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer. Sci Rep. 2016 Nov 8;6:36594.
Reference 2 Cucurbitacin D Overcomes Gefitinib Resistance by Blocking EGF Binding to EGFR and Inducing Cell Death in NSCLCs. Front Oncol. 2020 Feb 18;10:62.
Reference 3 Apoptosis induction through proteasome inhibitory activity of cucurbitacin D in human T-cell leukemia. Cancer. 2011 Jun 15;117(12):2735-46.
Reference 4 Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. Cancers (Basel). 2019 Mar 14;11(3):364.
Reference 5 Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer). Cells. 2019 Dec 31;9(1):103.
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