Natural Product (NP) Details

General Information of the NP (ID: NP7608)
Name
Piperine
Synonyms
piperine; 94-62-2; 1-Piperoylpiperidine; Piperin; Bioperine; Piperoylpiperidine; (E,E)-1-piperoylpiperidine; N-[(E,E)-Piperoyl]piperidine; Piperidine, 1-piperoyl-, (E,E)-; UNII-U71XL721QK; FEMA No. 2909; CCRIS 5572; Piperine (aliphatic); 1-Piperoylpiperidine, (E,E)-; 7780-20-3; C17H19NO3; EINECS 202-348-0; NSC 21727; 1-[(2E,4E)-5-(1,3-benzodioxol-5-yl)penta-2,4-dienoyl]piperidine; N-(E,E)-piperoyl-piperidine; CHEMBL43185; U71XL721QK; CHEBI:28821; MXXWOMGUGJBKIW-YPCIICBESA-N; NSC21727; piperidine, 1-[(2E,4E)-5-(1,3-benzodioxol-5-yl)
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Species Origin Piper nigrum ...     Click to Show/Hide
Piper nigrum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Piperales
Family: Piperaceae
Genus: Piper
Species: Piper nigrum
Piper longum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Piperales
Family: Piperaceae
Genus: Piper
Species: Piper longum
Disease Acquired hypomelanotic disorder [ICD-11: ED63] Phase 1/2 [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.731
 
MDCK Permeability
 -4.67
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 -0.194
 
PPB
 98%
 
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
 5.505
 
T1/2
 0.47
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
C17H19NO3
PubChem CID
638024
Canonical SMILES
C1CCN(CC1)C(=O)C=CC=CC2=CC3=C(C=C2)OCO3
InChI
1S/C17H19NO3/c19-17(18-10-4-1-5-11-18)7-3-2-6-14-8-9-15-16(12-14)21-13-20-15/h2-3,6-9,12H,1,4-5,10-11,13H2/b6-2+,7-3+
InChIKey
MXXWOMGUGJBKIW-YPCIICBESA-N
CAS Number
CAS 94-62-2
Herb ID
HBIN040071
ETMC ID
906
SymMap ID
SMIT00114
TCMSP ID
MOL001592
TTD Drug ID
D0H7PW
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Temozolomide      Brain 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 CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression CCNE1  Molecule Info 
Pathway MAP
Down-regulation Expression CDK2  Molecule Info 
Pathway MAP
Down-regulation Expression CDK4  Molecule Info 
Pathway MAP
Down-regulation Expression CDK6  Molecule Info 
Pathway MAP
                    In-vitro Model U-251MG CVCL_0021 Astrocytoma Homo sapiens
T98G CVCL_0556 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Piperine synergistically enhances the effect of temozolomide against temozolomide-resistant human glioma cell lines.
          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		 Down-regulation Phosphorylation RELA  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
4T1 CVCL_0125 Malignant neoplasms Mus musculus
                    In-vivo Model 1*105 4T1-luc murine cells were inoculated directly into the mouse mammary fat pad.
                    Experimental
                    Result(s)		 Piperine enhances TRAIL-based therapeutics for TNBC.
          Celecoxib      Rheumatoid arthritis     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		 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
Up-regulation Cleavage CASP7  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Expression CTNNB1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation GSK-3B  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression WNT3A  Molecule Info 
Pathway MAP
Down-regulation Expression WNT5A  Molecule Info 
Pathway MAP
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    In-vivo Model CT26.WT (5*106) cells were inoculated subcutaneously in female Balb/c mice.
                    Experimental
                    Result(s)		 Piperine and Celecoxib synergistically inhibit colon cancer cell proliferation via modulating Wnt/beta-catenin signaling pathway.
          Mitomycin C      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 [5]
                    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 Expression BID  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression RELA  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation STAT3  Molecule Info 
Pathway MAP
                    In-vitro Model HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
Ect1/E6E7 CVCL_3679 Healthy Homo sapiens
                    In-vivo Model 5*106 Hela/MMC cells were injected subcutaneously into the right oxter of mice.
                    Experimental
                    Result(s)		 Piperine potentiates MMC-induced anti-tumor effect on cervical cancer cells with drug resistance through blocking p-STAT3/p65 and Bcl-2 activation.
Target and Pathway
Target(s) Monoamine oxidase A (MAO-A)  Molecule Info  [6]
Monoamine oxidase B (MAO-B)  Molecule Info  [6]
BioCyc Superpathway of tryptophan utilization Click to Show/Hide
2 Dopamine degradation
3 Putrescine degradation III
4 Noradrenaline and adrenaline degradation
5 Serotonin degradation
6 Superpathway of melatonin degradation
7 Melatonin degradation II
8 Tryptophan degradation via tryptamine
KEGG Pathway Glycine, serine and threonine metabolism Click to Show/Hide
2 Arginine and proline metabolism
3 Histidine metabolism
4 Tyrosine metabolism
5 Phenylalanine metabolism
6 Tryptophan metabolism
7 Drug metabolism - cytochrome P450
8 Metabolic pathways
9 Serotonergic synapse
10 Dopaminergic synapse
11 Cocaine addiction
12 Amphetamine addiction
13 Alcoholism
NetPath Pathway IL4 Signaling Pathway Click to Show/Hide
Panther Pathway Adrenaline and noradrenaline biosynthesis Click to Show/Hide
2 5-Hydroxytryptamine degredation
3 Dopamine receptor mediated signaling pathway
Pathwhiz Pathway Histidine Metabolism Click to Show/Hide
2 Tyrosine Metabolism
3 Glycine and Serine Metabolism
Pathway Interaction Database Alpha-synuclein signaling Click to Show/Hide
Reactome Norepinephrine Neurotransmitter Release Cycle Click to Show/Hide
WikiPathways SIDS Susceptibility Pathways Click to Show/Hide
2 Biogenic Amine Synthesis
3 Oxidative Stress
4 Dopamine metabolism
5 Phase 1 - Functionalization of compounds
6 Neurotransmitter Release Cycle
7 Neurotransmitter Clearance In The Synaptic Cleft
8 Serotonin Transporter Activity
9 Tryptophan metabolism
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: 2489).
Reference 2 Piperine synergistically enhances the effect of temozolomide against temozolomide-resistant human glioma cell lines. Bioengineered. 2020 Dec;11(1):791-800.
Reference 3 Piperine enhances the efficacy of TRAIL-based therapy for triple-negative breast cancer cells. Anticancer Res. 2014 Apr;34(4):1893-9.
Reference 4 Piperine and Celecoxib synergistically inhibit colon cancer cell proliferation via modulating Wnt/beta-catenin signaling pathway. Phytomedicine. 2021 Apr;84:153484.
Reference 5 Piperine (PP) enhanced mitomycin-C (MMC) therapy of human cervical cancer through suppressing Bcl-2 signaling pathway via inactivating STAT3/NF-KappaB. Biomed Pharmacother. 2017 Dec;96:1403-1410.
Reference 6 Proposed structural basis of interaction of piperine and related compounds with monoamine oxidases. Bioorg Med Chem Lett. 2010 Jan 15;20(2):537-40.
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