Natural Product: NPC239808

Natural Product IDNPC239808
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YAICIVXHPPILRT-JVLMNHKTSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 102326871
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000037] Styrenes

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 YAICIVXHPPILRT-JVLMNHKTSA-N
Standard InCHI InChI=1S/C17H16O2/c18-16-10-6-14(7-11-16)4-2-1-3-5-15-8-12-17(19)13-9-15/h2-13,18-19H,1H2/b4-2-,5-3-
SMILES C(/C=Cc1ccc(cc1)O)/C=Cc1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   252.12 Volume:   281.964
?
Van der Waals volume.
Dense:   0.894 LogP:   4.342
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.868
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.293
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   14.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.855 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.222 Fsp3:   0.059
MCE-18:   10.0
?
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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.918 Fluc inhibitor:   0.992
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.013
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.367
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.998 Promiscuous compounds:   0.421

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.937 MDCK Permeability:   -4.767
Pgp-inhibitor:   0.05 Pgp-substrate:   0.004
PAMPA:   0.038
?
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):   0.004
20% Bioavailability (F20%):   0.918 30% Bioavailability (F30%):   0.906
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.015 MRP1:   0.483
Plasma Protein Binding (PPB):   97.022% Volume Distribution (VD):   0.073
Fu: 3.047%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.968
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.481
BSEP inhibitor:   0.857

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.006
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.822
CYP2C9-inhibitor:   0.024 CYP2C9-substrate:   0.205
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.985
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.206
?
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):  12.527 Half-life (T1/2):  0.971

ADMET: Toxicity

hERG Blockers:  0.967 hERG Blockers (10um):  0.951
Human Hepatotoxicity (H-HT):  0.856 Drug-induced Liver Injury (DILI):  0.0
AMES Toxicity:  0.532 Rat Oral Acute Toxicity:  0.029
Maximum Recommended Daily Dose:  0.531 Skin Sensitization:  1.0
Carcinogencity:  0.008 Eye Corrosion:  0.007
Eye Irritation:  0.997 Respiratory Toxicity:  0.853
Drug-induced Neurotoxicity:  0.648 Ototoxicity:  0.454
Hematotoxicity:  0.0 Drug-induced Nephrotoxicity:  0.056
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.011
A549 Cytotoxicity:  0.838 Hek293 Cytotoxicity:  0.429
BCF:   1.567
?
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:   4.458
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.501
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.11
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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
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota Leaves n.a. n.a. PMID[27140807]
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota leaves n.a. n.a. PMID[33127538]
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota fresh sarcotestas Kwanak Campus of Seoul National University, Seoul, Korea 1996-Sep PMID[9677265]
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota leaves St. Louis 1996-SEP PMID[9834151]
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. PMID[9834158]
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota Wood n.a. n.a. Database[FooDB]
NPO29719 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. Database[FooDB]

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
NPT2 Others Unspecified n.a. FC = 4.7 n.a. PMID[33127538]
NPT2 Others Unspecified n.a. FC = 7.8 n.a. PMID[33127538]

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 NPC239808 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
0.6923 Remote Similarity NPC248817
0.6552 Remote Similarity NPC286006
0.6207 Remote Similarity NPC104216
0.5938 Remote Similarity NPC68269
0.5806 Remote Similarity NPC181709
0.5769 Remote Similarity NPC265146
0.5625 Remote Similarity NPC184169
0.5294 Remote Similarity NPC82664
0.5294 Remote Similarity NPC253746
0.5294 Remote Similarity NPC132271
0.5294 Remote Similarity NPC98382
0.5294 Remote Similarity NPC292730
0.5294 Remote Similarity NPC216520
0.5294 Remote Similarity NPC17525
0.525 Remote Similarity NPC216468
0.525 Remote Similarity NPC78119
0.5135 Remote Similarity NPC51698
0.5122 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 NPC239808 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