Natural Product: NPC85479

Natural Product IDNPC85479
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-[(10Z,13Z,16Z)-Nonadeca-10,13,16-Trienyl]Benzene-1,3-Diol
IUPAC Name 5-[(10Z,13Z,16Z)-nonadeca-10,13,16-trienyl]benzene-1,3-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1795553
PubChem CID 53357975
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 KKVVRYFZFGBRPM-PDBXOOCHSA-N
Standard InCHI InChI=1S/C25H38O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-23-20-24(26)22-25(27)21-23/h3-4,6-7,9-10,20-22,26-27H,2,5,8,11-19H2,1H3/b4-3-,7-6-,10-9-
SMILES CC/C=CC/C=CC/C=CCCCCCCCCCc1cc(O)cc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.29 Volume:   434.161
?
Van der Waals volume.
Dense:   0.853 LogP:   9.282
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   5.16
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.764
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   15.0 Rigid Bonds:   9.0
TPSA:   40.46
?
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:   0.246 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.749 Fsp3:   0.52
MCE-18:   6.0
?
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:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.715 Fluc inhibitor:   0.29
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.137
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.814 Promiscuous compounds:   0.115

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.22 MDCK Permeability:   -4.813
Pgp-inhibitor:   0.639 Pgp-substrate:   0.0
PAMPA:   0.0
?
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):   0.0
20% Bioavailability (F20%):   0.772 30% Bioavailability (F30%):   0.916
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.054 MRP1:   0.988
Plasma Protein Binding (PPB):   99.145% Volume Distribution (VD):   0.76
Fu: 0.472%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.063
OATP1B3 inhibitor:   0.912 BCRP inhibitor:   0.867
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.012 CYP1A2-substrate:   0.988
CYP2C19-inhibitor:   0.034 CYP2C19-substrate:   0.343
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.662
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.999 CYP2C8-inhibitor:   1.0
HLM stability:   0.015
?
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):  4.752 Half-life (T1/2):  0.679

ADMET: Toxicity

hERG Blockers:  0.8 hERG Blockers (10um):  0.904
Human Hepatotoxicity (H-HT):  0.022 Drug-induced Liver Injury (DILI):  0.0
AMES Toxicity:  0.643 Rat Oral Acute Toxicity:  0.059
Maximum Recommended Daily Dose:  0.002 Skin Sensitization:  1.0
Carcinogencity:  0.001 Eye Corrosion:  1.0
Eye Irritation:  1.0 Respiratory Toxicity:  0.988
Drug-induced Neurotoxicity:  0.026 Ototoxicity:  0.024
Hematotoxicity:  0.0 Drug-induced Nephrotoxicity:  0.142
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.025
A549 Cytotoxicity:  0.824 Hek293 Cytotoxicity:  0.087
BCF:   1.353
?
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:   4.983
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.288
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.775
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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
NPO33268 wheat n.a. n.a. n.a. wheat germ n.a. n.a. PMID[19284743]
NPO33268 wheat n.a. n.a. n.a. wheat bran n.a. n.a. PMID[21658963]
NPO33268 wheat n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]

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
NPT393 Cell line HCT-116 Homo sapiens IC50 = 20.03 ug.mL-1 PMID[12444681]
NPT139 Cell line HT-29 Homo sapiens IC50 = 39.54 ug.mL-1 PMID[20439614]

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 NPC85479 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
1.0 High Similarity NPC242342
0.8947 High Similarity NPC71002
0.8947 High Similarity NPC302219
0.8947 High Similarity NPC249828
0.8462 Intermediate Similarity NPC10588
0.8378 Intermediate Similarity NPC53051
0.8378 Intermediate Similarity NPC24404
0.8378 Intermediate Similarity NPC313030
0.8333 Intermediate Similarity NPC470700
0.8333 Intermediate Similarity NPC54844
0.8333 Intermediate Similarity NPC39097
0.8333 Intermediate Similarity NPC302681
0.8333 Intermediate Similarity NPC118286
0.8333 Intermediate Similarity NPC109691
0.825 Intermediate Similarity NPC72947
0.8158 Intermediate Similarity NPC146798
0.8158 Intermediate Similarity NPC222522
0.8158 Intermediate Similarity NPC106396
0.8158 Intermediate Similarity NPC94351
0.8158 Intermediate Similarity NPC168303
0.7895 Intermediate Similarity NPC39664
0.775 Intermediate Similarity NPC166761
0.7174 Intermediate Similarity NPC61033
0.6744 Remote Similarity NPC284011
0.6667 Remote Similarity NPC210497
0.6667 Remote Similarity NPC246056
0.6591 Remote Similarity NPC158253
0.6579 Remote Similarity NPC294186
0.6579 Remote Similarity NPC147310
0.6579 Remote Similarity NPC137415
0.6579 Remote Similarity NPC166313
0.6579 Remote Similarity NPC192032
0.6579 Remote Similarity NPC24407
0.6579 Remote Similarity NPC11280
0.6458 Remote Similarity NPC305603
0.6304 Remote Similarity NPC192
0.6275 Remote Similarity NPC140521
0.6222 Remote Similarity NPC204901
0.6136 Remote Similarity NPC483454
0.6136 Remote Similarity NPC162314
0.6122 Remote Similarity NPC127894
0.6122 Remote Similarity NPC470759
0.6 Remote Similarity NPC94139
0.6 Remote Similarity NPC147284
0.5909 Remote Similarity NPC232523
0.5778 Remote Similarity NPC488413
0.5778 Remote Similarity NPC488412
0.5714 Remote Similarity NPC241891
0.5714 Remote Similarity NPC134829
0.5714 Remote Similarity NPC470760
0.566 Remote Similarity NPC123559
0.5625 Remote Similarity NPC48730
0.5556 Remote Similarity NPC486908
0.549 Remote Similarity NPC249836
0.5306 Remote Similarity NPC219070
0.5294 Remote Similarity NPC248396
0.5217 Remote Similarity NPC487734
0.52 Remote Similarity NPC471503
0.52 Remote Similarity NPC483450

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC85479 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