Natural Product: NPC193484

Natural Product IDNPC193484
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methysticin
IUPAC Name (2R)-2-[(E)-2-(1,3-benzodioxol-5-yl)ethenyl]-4-methoxy-2,3-dihydropyran-6-one
Synonyms (+)-Methysticin; Methylsticin; Methysticin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL579224
PubChem CID 5281567
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0001761] Kavalactones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey GTEXBOVBADJOQH-FWEMWIAWSA-N
Standard InCHI InChI=1S/C15H14O5/c1-17-12-7-11(20-15(16)8-12)4-2-10-3-5-13-14(6-10)19-9-18-13/h2-6,8,11H,7,9H2,1H3/b4-2+/t11-/m0/s1
SMILES COC1=CC(=O)O[C@@H](/C=C/c2ccc3c(c2)OCO3)C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.08 Volume:   270.459
?
Van der Waals volume.
Dense:   1.013 LogP:   2.136
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.334
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.948
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   53.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.791 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.281 Fsp3:   0.267
MCE-18:   49.737
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.805 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.225
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.201
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.544 Promiscuous compounds:   0.128

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.846 MDCK Permeability:   -4.751
Pgp-inhibitor:   0.029 Pgp-substrate:   0.006
PAMPA:   0.234
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.001
20% Bioavailability (F20%):   0.134 30% Bioavailability (F30%):   0.054
50% Bioavailability (F50%):   0.861

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.52 MRP1:   0.364
Plasma Protein Binding (PPB):   93.364% Volume Distribution (VD):   0.06
Fu: 7.659%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.954
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.071
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.493 CYP1A2-substrate:   0.883
CYP2C19-inhibitor:   0.113 CYP2C19-substrate:   0.017
CYP2C9-inhibitor:   0.051 CYP2C9-substrate:   0.942
CYP2D6-inhibitor:   0.863 CYP2D6-substrate:   0.995
CYP3A4-inhibitor:   0.005 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.826
HLM stability:   0.615
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  4.834 Half-life (T1/2):  0.834

ADMET: Toxicity

hERG Blockers:  0.088 hERG Blockers (10um):  0.389
Human Hepatotoxicity (H-HT):  0.629 Drug-induced Liver Injury (DILI):  0.884
AMES Toxicity:  0.722 Rat Oral Acute Toxicity:  0.332
Maximum Recommended Daily Dose:  0.696 Skin Sensitization:  0.971
Carcinogencity:  0.908 Eye Corrosion:  0.327
Eye Irritation:  0.962 Respiratory Toxicity:  0.23
Drug-induced Neurotoxicity:  0.691 Ototoxicity:  0.148
Hematotoxicity:  0.183 Drug-induced Nephrotoxicity:  0.856
Genotoxicity:  0.631 RPMI-8226 Immunitoxicity:  0.101
A549 Cytotoxicity:  0.167 Hek293 Cytotoxicity:  0.239
BCF:   1.295
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.703
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.824
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.849
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96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO26193 Piper methysticum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[11830162]
NPO26193 Piper methysticum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[12809361]
NPO26193 Piper methysticum Species Piperaceae Eukaryota root n.a. n.a. PMID[25597012]
NPO26193 Piper methysticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26193 Piper methysticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26193 Piper methysticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26193 Piper methysticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26193 Piper methysticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT153 Individual protein Androgen Receptor Homo sapiens Potency n.a. 6622.4 nM PubChem BioAssay data set
NPT210 Individual protein Thyroid stimulating hormone receptor Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 2511.9 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 6682.4 nM PubChem BioAssay data set
NPT158 Individual protein Nuclear receptor subfamily 1 group I member 2 Rattus norvegicus Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT103 Individual protein Nuclear receptor ROR-gamma Homo sapiens Potency n.a. 84.1 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 74978.0 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 125.9 nM PubChem BioAssay data set
NPT540 Individual protein Bile acid receptor FXR Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT67 Individual protein Cholinesterase Equus caballus Inhibition = 0.15 % PMID[23062825]
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 5011.9 nM PubChem BioAssay data set
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = -4.34 % PMID[23062825]
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT546 Individual protein Retinoid X receptor alpha Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT364 Organism Lactuca sativa Lactuca sativa Inhibition = 53.1 % PMID[16448174]
NPT364 Organism Lactuca sativa Lactuca sativa Inhibition = 61.2 % PMID[16448174]
NPT364 Organism Lactuca sativa Lactuca sativa Inhibition = 73.3 % PMID[16448174]
NPT364 Organism Lactuca sativa Lactuca sativa Inhibition = 71.1 % PMID[16448174]
NPT364 Organism Lactuca sativa Lactuca sativa Inhibition = 55.6 % PMID[16448174]
NPT364 Organism Lactuca sativa Lactuca sativa Inhibition = 48.1 % PMID[16448174]
NPT2567 Organism Trichoderma viride Hypocrea rufa GI = 0.0 % PMID[16448174]
NPT637 Organism Fusarium oxysporum Fusarium oxysporum GI = 36.2 % PMID[16448174]
NPT637 Organism Fusarium oxysporum Fusarium oxysporum GI = 11.6 % PMID[16448174]
NPT2600 Organism Fusarium solani Fusarium solani GI = 33.9 % PMID[16448174]
NPT2600 Organism Fusarium solani Fusarium solani GI = 37.1 % PMID[16448174]
NPT117 Organism Echinochloa crus-galli Echinochloa crus-galli Inhibition = 83.9 % PMID[16448174]
NPT117 Organism Echinochloa crus-galli Echinochloa crus-galli Inhibition = 75.4 % PMID[16448174]
NPT117 Organism Echinochloa crus-galli Echinochloa crus-galli Inhibition = 56.0 % PMID[16448174]
NPT117 Organism Echinochloa crus-galli Echinochloa crus-galli Inhibition = 55.0 % PMID[16448174]
NPT117 Organism Echinochloa crus-galli Echinochloa crus-galli Inhibition = 60.0 % PMID[16448174]
NPT117 Organism Echinochloa crus-galli Echinochloa crus-galli Inhibition = 50.0 % PMID[16448174]
NPT2 Others Unspecified n.a. Potency n.a. 9354.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 46882.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 65.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 10408.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 58.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 414.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 14825.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 10495.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 52603.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 41784.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 8267.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. IC50 = 0.19 ug.mL-1 PMID[19716299]
NPT562 Organism Colletotrichum gloeosporioides Colletotrichum gloeosporioides GI = 0.0 % PMID[16448174]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC193484 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.6154 Remote Similarity NPC169050
0.6154 Remote Similarity NPC286608
0.5833 Remote Similarity NPC85830
0.5769 Remote Similarity NPC212643
0.5357 Remote Similarity NPC199209
0.52 Remote Similarity NPC127326

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC193484 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.6154 Remote Similarity NPD1282 Approved

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data