Natural Product (NP) Details

General Information of the NP (ID: NP3369)
Name
Neferine
Synonyms
Neferine; 2292-16-2; Neferin; 4-[[(1R)-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl]methyl]-2-[[(1R)-6-methoxy-1-[(4-methoxyphenyl)methyl]-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl]oxy]phenol; BRN 1523459; CHEMBL455560; SCHEMBL12807595; DTXSID40177462; CHEBI:176257; ZINC6017976; AKOS016002114; Phenol, 4-((1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-isoquinolinyl)methyl)-2-((1,2,3,4-tetrahydro-6-methoxy-1-((4-methoxyphenyl)methyl)-2-methyl-7-isoquinolinyl)oxy)-; X1192; A14743; 292N162; Q-100292; 4-{[(1R)-6,7-Dimethoxy-2-methyl-1,2,3,4-tetrahydro-1-isoquinolinyl]methyl}-2-{[(1R)-6-methoxy-1-(4-methoxybenzyl)-2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl]oxy}phenol
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Species Origin Nelumbo nucifera ...     Click to Show/Hide
Nelumbo nucifera
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Proteales
Family: Nelumbonaceae
Genus: Nelumbo
Species: Nelumbo nucifera
Disease Lung cancer [ICD-11: 2C25] Investigative [1]
Structure
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2D MOL

3D MOL

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Formula
C38H44N2O6
PubChem CID
159654
Canonical SMILES
CN1CCC2=CC(=C(C=C2C1CC3=CC=C(C=C3)OC)OC4=C(C=CC(=C4)CC5C6=CC(=C(C=C6CCN5C)OC)OC)O)OC
InChI
1S/C38H44N2O6/c1-39-15-14-27-21-36(44-5)38(23-30(27)31(39)17-24-7-10-28(42-3)11-8-24)46-34-19-25(9-12-33(34)41)18-32-29-22-37(45-6)35(43-4)20-26(29)13-16-40(32)2/h7-12,19-23,31-32,41H,13-18H2,1-6H3/t31-,32-/m1/s1
InChIKey
MIBATSHDJRIUJK-ROJLCIKYSA-N
CAS Number
CAS 2292-16-2
ChEBI ID
CHEBI:176257
Herb ID
HBIN036518
SymMap ID
SMIT01524
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Oxaliplatin      Colorectal 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 [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CDH1  Molecule Info 
Pathway MAP
                    Experimental
                    Result(s)		 Snail overexpression or TGF-Beta1-induced EMT attenuated Neferine-mediated OXA sensitization in HCC.
          TNF-related apoptosis inducing ligand      Lung 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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
                    In-vitro Model DU145 CVCL_0105 Prostate carcinoma Homo sapiens
LNCaP CVCL_0395 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Neferine treatment effectively promotes TRAIL-mediated cell death and this effect likely occurs via the autophagic flux and the JNK pathway.
          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 [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model Bone marrow mononuclear cells derived from chronic myeloid leukemia patients Chronic myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 These results suggest that neferine might be a potential imatinib sensitizer in CML treatment.
          Cisplatin      Bladder 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 [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy via the AMPK/mTOR signaling pathway.
          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 [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Neferine acts as an effective enhancer of DOX-induced cell death in A549 cells through ROS mediated apoptosis with MAPK activation and inhibition of NF-KappaB nuclear translocation.
Target and Pathway
Target(s) Nuclear factor erythroid 2-related factor 2 (Nrf2)  Molecule Info  [7]
Ribosomal protein S6 kinase beta-1 (S6K1)  Molecule Info  [8]
KEGG Pathway Protein processing in endoplasmic reticulum Click to Show/Hide
2 ErbB signaling pathway
3 HIF-1 signaling pathway
4 mTOR signaling pathway
5 PI3K-Akt signaling pathway
6 AMPK signaling pathway
7 TGF-beta signaling pathway
8 Fc gamma R-mediated phagocytosis
9 Insulin signaling pathway
10 Proteoglycans in cancer
11 Acute myeloid leukemia
12 Choline metabolism in cancer
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
Panther Pathway Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade Click to Show/Hide
2 PDGF signaling pathway
3 PI3 kinase pathway
4 p53 pathway by glucose deprivation
5 CCKR signaling map ST
Pathwhiz Pathway Leucine Stimulation on Insulin Signaling Click to Show/Hide
Pathway Interaction Database Insulin Pathway Click to Show/Hide
2 IL4-mediated signaling events
3 CDC42 signaling events
4 Angiopoietin receptor Tie2-mediated signaling
5 Regulation of Telomerase
6 mTOR signaling pathway
7 IGF1 pathway
8 IL2 signaling events mediated by PI3K
9 Integrins in angiogenesis
10 RXR and RAR heterodimerization with other nuclear receptor
11 Signaling events mediated by Stem cell factor receptor (c-Kit)
12 a6b1 and a6b4 Integrin signaling
13 TGF-beta receptor signaling
Reactome mTORC1-mediated signalling Click to Show/Hide
WikiPathways Oxidative Stress Click to Show/Hide
2 Transcriptional activation by NRF2
3 NRF2 pathway
4 Nuclear Receptors Meta-Pathway
5 Aryl Hydrocarbon Receptor Pathway
6 Mesodermal Commitment Pathway
7 Aryl Hydrocarbon Receptor
8 Quercetin and Nf-kB/ AP-1 Induced Cell Apoptosis
9 Arylhydrocarbon receptor (AhR) signaling pathway
10 ErbB Signaling Pathway
11 Interferon type I signaling pathways
12 G13 Signaling Pathway
13 IL-2 Signaling Pathway
14 Insulin Signaling
15 Cytoplasmic Ribosomal Proteins
16 EGF/EGFR Signaling Pathway
17 IL-4 Signaling Pathway
18 IL-6 signaling pathway
19 Kit receptor signaling pathway
20 Apoptosis-related network due to altered Notch3 in ovarian cancer
21 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
22 BDNF signaling pathway
23 Interleukin-11 Signaling Pathway
24 FSH signaling pathway
25 Leptin signaling pathway
26 TSH signaling pathway
27 Signaling by Insulin receptor
28 TOR Signaling
29 AMPK Signaling
30 IL-5 Signaling Pathway
References
Reference 1 Neferine suppresses diethylnitrosamine-induced lung carcinogenesis in Wistar rats. Food Chem Toxicol. 2019 Jan;123:385-398.
Reference 2 The anti-tumor activities of Neferine on cell invasion and oxaliplatin sensitivity regulated by EMT via Snail signaling in hepatocellular carcinoma. Sci Rep. 2017 Jan 30;7:41616.
Reference 3 Neferine treatment enhances the TRAIL?induced apoptosis of human prostate cancer cells via autophagic flux and the JNK pathway. Int J Oncol. 2020 May;56(5):1152-1161.
Reference 4 Neferine in the Lotus Plumule Potentiates the Antitumor Effect of Imatinib in Primary Chronic Myeloid Leukemia Cells In Vitro. J Food Sci. 2019 Apr;84(4):904-910.
Reference 5 Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy via the AMPK/mTOR signaling pathway. Biochem Biophys Res Commun. 2017 Mar 11;484(3):694-701.
Reference 6 Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells. Food Chem Toxicol. 2014 Jun;68:87-98.
Reference 7 Mitochondrial protective effect of neferine through the modulation of nuclear factor erythroid 2-related factor 2 signalling in ischaemic stroke. Br J Pharmacol. 2019 Feb;176(3):400-415.
Reference 8 Anti-angiogenesis effect of Neferine via regulating autophagy and polarization of tumor-associated macrophages in high-grade serous ovarian carcinoma. Cancer Lett. 2018 Sep 28;432:144-155.
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