Natural Product: NPC102639

Natural Product IDNPC102639
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Longistyline C
IUPAC Name 3-methoxy-4-(3-methylbut-2-enyl)-5-[(E)-2-phenylethenyl]phenol
Synonyms Longistyline C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL445702
PubChem CID 6446720
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000253] Stilbenes

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 NFAWEPOBHKEHPO-ZHACJKMWSA-N
Standard InCHI InChI=1S/C20H22O2/c1-15(2)9-12-19-17(13-18(21)14-20(19)22-3)11-10-16-7-5-4-6-8-16/h4-11,13-14,21H,12H2,1-3H3/b11-10+
SMILES COc1cc(O)cc(c1CC=C(C)C)/C=C/c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   294.16 Volume:   333.852
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Van der Waals volume.
Dense:   0.881 LogP:   5.544
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.369
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.217
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   29.46
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.615 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.426 Fsp3:   0.2
MCE-18:   12.0
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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:   0.991 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:   0.368
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.848
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.726 Promiscuous compounds:   0.092

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.016 MDCK Permeability:   -4.794
Pgp-inhibitor:   0.291 Pgp-substrate:   0.007
PAMPA:   0.096
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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):   0.003
20% Bioavailability (F20%):   0.936 30% Bioavailability (F30%):   0.981
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.454
Plasma Protein Binding (PPB):   96.426% Volume Distribution (VD):   0.455
Fu: 3.219%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.818
BSEP inhibitor:   0.654

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.397 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.34 CYP2C9-substrate:   0.733
CYP2D6-inhibitor:   0.991 CYP2D6-substrate:   0.209
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  12.595 Half-life (T1/2):  0.895

ADMET: Toxicity

hERG Blockers:  0.242 hERG Blockers (10um):  0.697
Human Hepatotoxicity (H-HT):  0.711 Drug-induced Liver Injury (DILI):  0.364
AMES Toxicity:  0.661 Rat Oral Acute Toxicity:  0.575
Maximum Recommended Daily Dose:  0.753 Skin Sensitization:  0.932
Carcinogencity:  0.431 Eye Corrosion:  0.001
Eye Irritation:  0.819 Respiratory Toxicity:  0.834
Drug-induced Neurotoxicity:  0.767 Ototoxicity:  0.324
Hematotoxicity:  0.189 Drug-induced Nephrotoxicity:  0.504
Genotoxicity:  0.632 RPMI-8226 Immunitoxicity:  0.057
A549 Cytotoxicity:  0.373 Hek293 Cytotoxicity:  0.625
BCF:   2.267
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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:   4.693
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.327
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.88
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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
NPO27986 Lonchocarpus chiricanus Species Fabaceae Eukaryota Root barks n.a. n.a. PMID[11421729]
NPO27806 Gossypium hirsutum Species Malvaceae Eukaryota n.a. n.a. n.a. PMID[37218075]
NPO27806 Gossypium hirsutum Species Malvaceae Eukaryota n.a. n.a. n.a. PMID[37513254]
NPO27684 Stoebe plumosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27932 Schistocarpha bicolor Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27986 Lonchocarpus chiricanus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27619 Dianella laevis Species Hydrobiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4643 Cladophora prolifera Species Cladophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27806 Gossypium hirsutum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27806 Gossypium hirsutum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27806 Gossypium hirsutum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27619 Dianella laevis Species Hydrobiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4643 Cladophora prolifera Species Cladophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27932 Schistocarpha bicolor Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27684 Stoebe plumosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27806 Gossypium hirsutum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27986 Lonchocarpus chiricanus Species Fabaceae 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
NPT1381 Organism Aedes aegypti Aedes aegypti Activity = 50.0 ppm PMID[11421729]

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 NPC102639 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
0.6792 Remote Similarity NPC105031
0.6346 Remote Similarity NPC488749
0.5926 Remote Similarity NPC606674
0.549 Remote Similarity NPC5503
0.5345 Remote Similarity NPC480994
0.5098 Remote Similarity NPC19808
0.5098 Remote Similarity NPC94045

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC102639 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