Natural Product: NPC586195

Natural Product IDNPC586195
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Gancaonin M
IUPAC Name 5,7-dihydroxy-3-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 DDLPIQXHEKZHQX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O5/c1-12(2)4-9-15-17(22)10-18(23)19-20(24)16(11-26-21(15)19)13-5-7-14(25-3)8-6-13/h4-8,10-11,22-23H,9H2,1-3H3
SMILES COC1=CC=C(C2=COC3=C(CC=C(C)C)C(O)=CC(O)=C3C2=O)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   352.13 Volume:   366.326
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Van der Waals volume.
Dense:   0.961 LogP:   3.937
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.324
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.546
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   79.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.681 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.602 Fsp3:   0.19
MCE-18:   19.0
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.872 Fluc inhibitor:   0.795
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.977
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.715
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.284 Promiscuous compounds:   0.243

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.884 MDCK Permeability:   -4.621
Pgp-inhibitor:   0.709 Pgp-substrate:   0.093
PAMPA:   0.18
?
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):   0.108
20% Bioavailability (F20%):   0.729 30% Bioavailability (F30%):   0.93
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.815
Plasma Protein Binding (PPB):   95.733% Volume Distribution (VD):   0.277
Fu: 3.534%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.977 BCRP inhibitor:   0.977
BSEP inhibitor:   0.907

ADMET: Metabolism

CYP1A2-inhibitor:   0.626 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.947
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.131
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.06 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):  4.433 Half-life (T1/2):  1.133

ADMET: Toxicity

hERG Blockers:  0.099 hERG Blockers (10um):  0.539
Human Hepatotoxicity (H-HT):  0.548 Drug-induced Liver Injury (DILI):  0.957
AMES Toxicity:  0.717 Rat Oral Acute Toxicity:  0.746
Maximum Recommended Daily Dose:  0.661 Skin Sensitization:  0.643
Carcinogencity:  0.613 Eye Corrosion:  0.0
Eye Irritation:  0.737 Respiratory Toxicity:  0.958
Drug-induced Neurotoxicity:  0.401 Ototoxicity:  0.347
Hematotoxicity:  0.256 Drug-induced Nephrotoxicity:  0.584
Genotoxicity:  0.951 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.314 Hek293 Cytotoxicity:  0.533
BCF:   1.863
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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:   4.763
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.231
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.681
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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
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11164-015-2099-x]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443711030101]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[16441081]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16675659]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[22074222]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22074222]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. rhizome n.a. PMID[23867078]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[23867078]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24479468]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota roots n.a. n.a. PMID[24957203]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25445757]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25744461]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[26841168]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[32196343]
NPO4095 Hedysarum multijugum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4095 Hedysarum multijugum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4095 Hedysarum multijugum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7154 Glycyrrhiza uralensis 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

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 NPC586195 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
0.8254 Intermediate Similarity NPC604255
0.7705 Intermediate Similarity NPC144118
0.7576 Intermediate Similarity NPC610891
0.7302 Intermediate Similarity NPC38545
0.7121 Intermediate Similarity NPC130589
0.6986 Remote Similarity NPC349624
0.697 Remote Similarity NPC80962
0.6716 Remote Similarity NPC169162
0.6667 Remote Similarity NPC40868
0.6567 Remote Similarity NPC92075
0.6479 Remote Similarity NPC78103
0.6471 Remote Similarity NPC40942
0.6418 Remote Similarity NPC273538
0.625 Remote Similarity NPC611367
0.5915 Remote Similarity NPC233918
0.5882 Remote Similarity NPC478987
0.5846 Remote Similarity NPC294409
0.5846 Remote Similarity NPC490701
0.5775 Remote Similarity NPC193564
0.5733 Remote Similarity NPC604254
0.5714 Remote Similarity NPC222298
0.5714 Remote Similarity NPC604003
0.56 Remote Similarity NPC256406
0.5571 Remote Similarity NPC204985
0.5541 Remote Similarity NPC476178
0.5455 Remote Similarity NPC116632
0.5417 Remote Similarity NPC606794
0.5352 Remote Similarity NPC606446
0.5342 Remote Similarity NPC133400
0.5278 Remote Similarity NPC171916
0.527 Remote Similarity NPC268059
0.5263 Remote Similarity NPC117836
0.5224 Remote Similarity NPC35763
0.52 Remote Similarity NPC128774
0.5135 Remote Similarity NPC249824
0.5135 Remote Similarity NPC219917
0.5135 Remote Similarity NPC479160
0.5065 Remote Similarity NPC237635

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC586195 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
0.6418 Remote Similarity NPD4378 Phase 3

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