Natural Product: NPC303671

Natural Product IDNPC303671
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FISBBPCLKKQWQA-GQCTYLIASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11572851
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 FISBBPCLKKQWQA-GQCTYLIASA-N
Standard InCHI InChI=1S/C16H18O5/c1-18-13-9-12(21-16(17)10-13)6-4-11-5-7-14(19-2)15(8-11)20-3/h4-8,10,12H,9H2,1-3H3/b6-4+
SMILES COC1=CC(=O)OC(/C=C/c2ccc(c(c2)OC)OC)C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.12 Volume:   296.312
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Van der Waals volume.
Dense:   0.979 LogP:   2.138
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.374
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.829
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   53.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.78 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.062 Fsp3:   0.312
MCE-18:   38.286
?
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:   0.438 Fluc inhibitor:   0.878
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.109
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.38
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.562 Promiscuous compounds:   0.016

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.796 MDCK Permeability:   -4.594
Pgp-inhibitor:   0.6 Pgp-substrate:   0.008
PAMPA:   0.012
?
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):   0.106
20% Bioavailability (F20%):   0.098 30% Bioavailability (F30%):   0.228
50% Bioavailability (F50%):   0.691

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.012 MRP1:   0.111
Plasma Protein Binding (PPB):   90.908% Volume Distribution (VD):   0.057
Fu: 6.507%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.949
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.819 CYP1A2-substrate:   0.255
CYP2C19-inhibitor:   0.923 CYP2C19-substrate:   0.023
CYP2C9-inhibitor:   0.181 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.379 CYP2D6-substrate:   0.784
CYP3A4-inhibitor:   0.688 CYP3A4-substrate:   0.076
CYP2B6-substrate:   0.019 CYP2C8-inhibitor:   0.979
HLM stability:   0.87
?
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):  7.866 Half-life (T1/2):  1.173

ADMET: Toxicity

hERG Blockers:  0.086 hERG Blockers (10um):  0.503
Human Hepatotoxicity (H-HT):  0.601 Drug-induced Liver Injury (DILI):  0.778
AMES Toxicity:  0.575 Rat Oral Acute Toxicity:  0.172
Maximum Recommended Daily Dose:  0.542 Skin Sensitization:  0.971
Carcinogencity:  0.679 Eye Corrosion:  0.203
Eye Irritation:  0.955 Respiratory Toxicity:  0.366
Drug-induced Neurotoxicity:  0.777 Ototoxicity:  0.183
Hematotoxicity:  0.194 Drug-induced Nephrotoxicity:  0.71
Genotoxicity:  0.336 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.078 Hek293 Cytotoxicity:  0.217
BCF:   1.037
?
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:   3.597
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.403
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.621
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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

In vitro activity

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

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 NPC303671 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
0.8163 Intermediate Similarity NPC193484
0.6809 Remote Similarity NPC169050
0.6809 Remote Similarity NPC286608
0.5111 Remote Similarity NPC310905

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC303671 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
0.6809 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