Natural Product: NPC472364

Natural Product IDNPC472364
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PTQXQIDDMDYWCX-VOTSOKGWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3393845
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003472] 2'-Hydroxychalcones

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 PTQXQIDDMDYWCX-VOTSOKGWSA-N
Standard InCHI InChI=1S/C17H16O5/c1-21-13-9-15(20)17(16(10-13)22-2)14(19)7-6-11-4-3-5-12(18)8-11/h3-10,18,20H,1-2H3/b7-6+
SMILES COc1cc(O)c(c(c1)OC)C(=O)/C=C/c1cccc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   308.335
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Van der Waals volume.
Dense:   0.973 LogP:   2.902
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.124
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.9
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.655 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.204 Fsp3:   0.118
MCE-18:   13.0
?
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:   0.776 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.446
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.843
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.581 Promiscuous compounds:   0.641

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.885 MDCK Permeability:   -4.835
Pgp-inhibitor:   0.42 Pgp-substrate:   0.004
PAMPA:   0.008
?
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):   0.006
20% Bioavailability (F20%):   0.2 30% Bioavailability (F30%):   0.497
50% Bioavailability (F50%):   0.936

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.009
Plasma Protein Binding (PPB):   95.393% Volume Distribution (VD):   -0.395
Fu: 4.556%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.839
BSEP inhibitor:   0.918

ADMET: Metabolism

CYP1A2-inhibitor:   0.056 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.911
CYP2C9-inhibitor:   0.988 CYP2C9-substrate:   0.935
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.969
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.411
?
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):  8.258 Half-life (T1/2):  0.776

ADMET: Toxicity

hERG Blockers:  0.21 hERG Blockers (10um):  0.535
Human Hepatotoxicity (H-HT):  0.57 Drug-induced Liver Injury (DILI):  0.5
AMES Toxicity:  0.441 Rat Oral Acute Toxicity:  0.191
Maximum Recommended Daily Dose:  0.598 Skin Sensitization:  0.675
Carcinogencity:  0.349 Eye Corrosion:  0.05
Eye Irritation:  0.978 Respiratory Toxicity:  0.686
Drug-induced Neurotoxicity:  0.595 Ototoxicity:  0.223
Hematotoxicity:  0.225 Drug-induced Nephrotoxicity:  0.375
Genotoxicity:  0.456 RPMI-8226 Immunitoxicity:  0.107
A549 Cytotoxicity:  0.241 Hek293 Cytotoxicity:  0.547
BCF:   1.302
?
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:   4.051
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.244
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.75
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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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 9900.0 nM PMID[25597012]

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 NPC472364 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
0.7917 Intermediate Similarity NPC471417
0.7872 Intermediate Similarity NPC188646
0.7708 Intermediate Similarity NPC263670
0.74 Intermediate Similarity NPC473391
0.7292 Intermediate Similarity NPC242294
0.6863 Remote Similarity NPC337373
0.6731 Remote Similarity NPC472365
0.6538 Remote Similarity NPC476333
0.6538 Remote Similarity NPC175098
0.6538 Remote Similarity NPC472366
0.6296 Remote Similarity NPC119663
0.6182 Remote Similarity NPC472367
0.6182 Remote Similarity NPC472368
0.614 Remote Similarity NPC606423
0.6038 Remote Similarity NPC87231
0.6 Remote Similarity NPC212631
0.6 Remote Similarity NPC608685
0.5741 Remote Similarity NPC56031
0.5741 Remote Similarity NPC129132
0.5636 Remote Similarity NPC102003
0.5577 Remote Similarity NPC13238
0.5556 Remote Similarity NPC284556
0.5556 Remote Similarity NPC477243
0.5472 Remote Similarity NPC336114
0.5472 Remote Similarity NPC64359
0.5455 Remote Similarity NPC119660
0.5455 Remote Similarity NPC92722
0.537 Remote Similarity NPC205468
0.5357 Remote Similarity NPC150399
0.5273 Remote Similarity NPC312318
0.5273 Remote Similarity NPC308037
0.5273 Remote Similarity NPC265045
0.5273 Remote Similarity NPC605344
0.5179 Remote Similarity NPC301178
0.5106 Remote Similarity NPC305518
0.5094 Remote Similarity NPC139813
0.5091 Remote Similarity NPC469526

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472364 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
NPD

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