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Natural Product (NP) Details

General Information of the NP (ID: NP9745)
Name
Picropodophyllin
Synonyms
BVT-51004; IGF-1 inhibitors, Axelar/Biovitrum; IGF-1 inhibitors, Karolinska/Biovitrum; Insulin-like growth factor 1 inhibitors, Axelar/Biovitrum
    Click to Show/Hide
Species Origin Podophyllum peltatum ...     Click to Show/Hide
Podophyllum peltatum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Berberidaceae
Genus: Podophyllum
Species: Podophyllum peltatum
Diphylleia grayi
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Berberidaceae
Genus: Diphylleia
Species: Diphylleia grayi
Dysosma majoensis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Berberidaceae
Genus: Dysosma
Species: Dysosma majoensis
Juniperus thurifera
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Pinopsida
Family: Cupressaceae
Genus: Juniperus
Species: Juniperus thurifera
Juniperus sabina
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Pinopsida
Family: Cupressaceae
Genus: Juniperus
Species: Juniperus sabina
Diphylleia sinensis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Berberidaceae
Genus: Diphylleia
Species: Diphylleia sinensis
Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z] Phase 2 [1]
Structure
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2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C22H22O8
PubChem CID
72435
Canonical SMILES
COC1=CC(=CC(=C1OC)OC)C2C3C(COC3=O)C(C4=CC5=C(C=C24)OCO5)O
InChI
1S/C22H22O8/c1-25-16-4-10(5-17(26-2)21(16)27-3)18-11-6-14-15(30-9-29-14)7-12(11)20(23)13-8-28-22(24)19(13)18/h4-7,13,18-20,23H,8-9H2,1-3H3/t13-,18+,19+,20-/m0/s1
InChIKey
YJGVMLPVUAXIQN-HAEOHBJNSA-N
CAS Number
CAS 477-47-4
Herb ID
HBIN039888
ETMC ID
6101
SymMap ID
SMIT00475
TCMSP ID
MOL001710
TTD Drug ID
D01SJS
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Sorafenib      Renal cell carcinoma     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
                    In-vitro Model HLF CVCL_2947 Adult hepatocellular carcinoma Homo sapiens
PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)
Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells.
Target and Pathway
Target(s) Insulin-like growth factor I receptor (IGF1R)  Molecule Info  [3]
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
Reactome IRS-related events triggered by IGF1R Click to Show/Hide
2 SHC-related events triggered by IGF1R
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
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7873).
Reference 2 Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. Oncol Lett. 2014 Nov;8(5):2023-2026.
Reference 3 Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor: experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol. 2011 Apr;50(3):441-7.
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Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China