Natural Product: NPC158253

Natural Product IDNPC158253
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-Methyl-5-{8(Z),11(Z)-Pentadecadienyl}Resorcinol
IUPAC Name 2-methyl-5-[(8Z,11Z)-pentadeca-8,11-dienyl]benzene-1,3-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL470555
PubChem CID 5319544
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000134] Phenols
        • [CHEMONTID:0001286] Benzenediols
          • [CHEMONTID:0000137] Resorcinols

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 IZGYQWUVUWZOPQ-AFJQJTPPSA-N
Standard InCHI InChI=1S/C22H34O2/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-20-17-21(23)19(2)22(24)18-20/h5-6,8-9,17-18,23-24H,3-4,7,10-16H2,1-2H3/b6-5-,9-8-
SMILES CCC/C=CC/C=CCCCCCCCc1cc(O)c(c(c1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.26 Volume:   384.91
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Van der Waals volume.
Dense:   0.858 LogP:   8.33
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.705
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.682
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The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   8.0
TPSA:   40.46
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.335 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.634 Fsp3:   0.545
MCE-18:   7.0
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.857 Fluc inhibitor:   0.295
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.211
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.91 Promiscuous compounds:   0.04

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.059 MDCK Permeability:   -4.75
Pgp-inhibitor:   0.732 Pgp-substrate:   0.001
PAMPA:   0.002
?
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%):   0.86 30% Bioavailability (F30%):   0.944
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.062 MRP1:   0.973
Plasma Protein Binding (PPB):   99.02% Volume Distribution (VD):   0.531
Fu: 0.73%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.749
OATP1B3 inhibitor:   0.796 BCRP inhibitor:   0.649
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.855
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.972
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.18 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.059 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   1.0
HLM stability:   0.106
?
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):  6.345 Half-life (T1/2):  0.34

ADMET: Toxicity

hERG Blockers:  0.389 hERG Blockers (10um):  0.809
Human Hepatotoxicity (H-HT):  0.256 Drug-induced Liver Injury (DILI):  0.0
AMES Toxicity:  0.403 Rat Oral Acute Toxicity:  0.082
Maximum Recommended Daily Dose:  0.015 Skin Sensitization:  1.0
Carcinogencity:  0.005 Eye Corrosion:  1.0
Eye Irritation:  1.0 Respiratory Toxicity:  0.991
Drug-induced Neurotoxicity:  0.021 Ototoxicity:  0.14
Hematotoxicity:  0.001 Drug-induced Nephrotoxicity:  0.219
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.95 Hek293 Cytotoxicity:  0.311
BCF:   1.68
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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:   4.949
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.14
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.712
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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
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota Fruits n.a. n.a. PMID[8021657]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12510 Aronia arbutifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13070 Clibadium mexiae Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1744 Discaria serratifolia Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11636 Ideopsis similis Species Nymphalidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO998 Justicia hayatai Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3469 Pteris dactylina Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9180 Pyrostegia venusta Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3580 Rana amurensis Species Ranidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13016 Viscaria viscosa Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3580 Rana amurensis Species Ranidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3469 Pteris dactylina Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3580 Rana amurensis Species Ranidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1744 Discaria serratifolia Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9180 Pyrostegia venusta Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO998 Justicia hayatai Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3580 Rana amurensis Species Ranidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8896 Anacardium occidentale Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13016 Viscaria viscosa Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11636 Ideopsis similis Species Nymphalidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3469 Pteris dactylina Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12510 Aronia arbutifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13070 Clibadium mexiae Species Asteraceae 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
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = 20.0 % PMID[8021657]

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 NPC158253 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
0.8684 High Similarity NPC232523
0.85 High Similarity NPC204901
0.7381 Intermediate Similarity NPC302219
0.6977 Remote Similarity NPC71002
0.6977 Remote Similarity NPC249828
0.6591 Remote Similarity NPC242342
0.6591 Remote Similarity NPC85479
0.6522 Remote Similarity NPC210497
0.6429 Remote Similarity NPC53051
0.6429 Remote Similarity NPC24404
0.6429 Remote Similarity NPC313030
0.6279 Remote Similarity NPC146798
0.6279 Remote Similarity NPC222522
0.6279 Remote Similarity NPC106396
0.6279 Remote Similarity NPC94351
0.6279 Remote Similarity NPC168303
0.6222 Remote Similarity NPC10588
0.617 Remote Similarity NPC48730
0.6087 Remote Similarity NPC72947
0.6 Remote Similarity NPC488413
0.6 Remote Similarity NPC166761
0.6 Remote Similarity NPC488412
0.5952 Remote Similarity NPC470700
0.5952 Remote Similarity NPC54844
0.5952 Remote Similarity NPC39097
0.5952 Remote Similarity NPC302681
0.5952 Remote Similarity NPC118286
0.5952 Remote Similarity NPC109691
0.5682 Remote Similarity NPC39664
0.5652 Remote Similarity NPC483454
0.5652 Remote Similarity NPC162314
0.5532 Remote Similarity NPC94139
0.5532 Remote Similarity NPC147284
0.551 Remote Similarity NPC192
0.5476 Remote Similarity NPC59506
0.5208 Remote Similarity NPC129373
0.5208 Remote Similarity NPC488416
0.5192 Remote Similarity NPC248396
0.5116 Remote Similarity NPC37802
0.5106 Remote Similarity NPC196479
0.5106 Remote Similarity NPC487734
0.5094 Remote Similarity NPC305603

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC158253 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