Natural Product: NPC19290

Natural Product IDNPC19290
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (4E,6E)-1-(4-Hydroxyphenyl)-7-(4-Methoxyphenyl)Hepta-4,6-Dien-3-One
IUPAC Name (4E,6E)-1-(4-hydroxyphenyl)-7-(4-methoxyphenyl)hepta-4,6-dien-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2398586
PubChem CID 73353552
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids

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 LIAJVWYMSGZMPR-ZUVMSYQZSA-N
Standard InCHI InChI=1S/C20H20O3/c1-23-20-14-9-16(10-15-20)4-2-3-5-18(21)11-6-17-7-12-19(22)13-8-17/h2-5,7-10,12-15,22H,6,11H2,1H3/b4-2+,5-3+
SMILES COc1ccc(/C=C/C=C/C(=O)CCc2ccc(cc2)O)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   308.14 Volume:   340.006
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Van der Waals volume.
Dense:   0.906 LogP:   3.395
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.532
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.924
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   15.0
TPSA:   46.53
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.617 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.172 Fsp3:   0.15
MCE-18:   11.0
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.998 Fluc inhibitor:   0.998
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.045
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.92
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.872 Promiscuous compounds:   0.307

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.88 MDCK Permeability:   -4.807
Pgp-inhibitor:   0.99 Pgp-substrate:   0.001
PAMPA:   0.075
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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%):   0.839 30% Bioavailability (F30%):   0.955
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.0
Plasma Protein Binding (PPB):   97.186% Volume Distribution (VD):   -0.441
Fu: 2.31%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.422
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.157 CYP1A2-substrate:   0.872
CYP2C19-inhibitor:   0.044 CYP2C19-substrate:   0.921
CYP2C9-inhibitor:   0.029 CYP2C9-substrate:   0.123
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.863
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.991
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.736
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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):  11.033 Half-life (T1/2):  0.583

ADMET: Toxicity

hERG Blockers:  0.637 hERG Blockers (10um):  0.709
Human Hepatotoxicity (H-HT):  0.635 Drug-induced Liver Injury (DILI):  0.217
AMES Toxicity:  0.691 Rat Oral Acute Toxicity:  0.188
Maximum Recommended Daily Dose:  0.634 Skin Sensitization:  0.955
Carcinogencity:  0.361 Eye Corrosion:  0.011
Eye Irritation:  0.874 Respiratory Toxicity:  0.661
Drug-induced Neurotoxicity:  0.557 Ototoxicity:  0.365
Hematotoxicity:  0.143 Drug-induced Nephrotoxicity:  0.354
Genotoxicity:  0.206 RPMI-8226 Immunitoxicity:  0.059
A549 Cytotoxicity:  0.247 Hek293 Cytotoxicity:  0.789
BCF:   1.383
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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:   4.306
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.683
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.252
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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
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota rhizomes n.a. n.a. PMID[23707257]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14409 Dioscorea nipponica Species Dioscoreaceae 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
NPT34 Cell line BV-2 Mus musculus Activity = 18.5 % PMID[17043131]
NPT34 Cell line BV-2 Mus musculus IC50 = 8440.0 nM PMID[10498214]

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 NPC19290 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
0.8222 Intermediate Similarity NPC69332
0.7708 Intermediate Similarity NPC95178
0.7647 Intermediate Similarity NPC485985
0.7358 Intermediate Similarity NPC151167
0.72 Intermediate Similarity NPC277394
0.6364 Remote Similarity NPC276466
0.6154 Remote Similarity NPC299252
0.5918 Remote Similarity NPC139901
0.5517 Remote Similarity NPC218323
0.54 Remote Similarity NPC29989
0.537 Remote Similarity NPC88141
0.5273 Remote Similarity NPC70843
0.5263 Remote Similarity NPC23402
0.5172 Remote Similarity NPC123228
0.5172 Remote Similarity NPC123722
0.5098 Remote Similarity NPC201967
0.5091 Remote Similarity NPC120693

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC19290 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