Natural Product (NP) Details
| General Information of the NP (ID: NP9745) | |||||
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| Name |
Picropodophyllin
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| Synonyms |
BVT-51004; IGF-1 inhibitors, Axelar/Biovitrum; IGF-1 inhibitors, Karolinska/Biovitrum; Insulin-like growth factor 1 inhibitors, Axelar/Biovitrum
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| Species Origin | Podophyllum peltatum ... | Click to Show/Hide | |||
| Podophyllum peltatum | |||||
| Diphylleia grayi | |||||
| Dysosma majoensis | |||||
| Juniperus thurifera | |||||
| Juniperus sabina | |||||
| Diphylleia sinensis | |||||
| Disease | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | Phase 2 | [1] | ||
| Structure |
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Click to Download Mol2D MOL |
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| ADMET Property |
Absporption
Caco-2 Permeability
-5.008
MDCK Permeability
-4.764
PAMPA
- -
HIA
- - -
Distribution
VDss
-0.231
PPB
95.3%
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
4.07
T1/2
2.603
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 |
C22H22O8
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| PubChem CID | |||||
| Canonical SMILES |
COC1=CC(=CC(=C1OC)OC)C2C3C(COC3=O)C(C4=CC5=C(C=C24)OCO5)O
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| 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
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| InChIKey |
YJGVMLPVUAXIQN-HAEOHBJNSA-N
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| CAS Number |
CAS 477-47-4
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| Herb ID | |||||
| ETMC ID | |||||
| SymMap ID | |||||
| TCMSP ID | |||||
| TTD Drug ID | |||||
| 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
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| 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 | ||||
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| 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 | |||
