Natural Product: NPC518316

Natural Product IDNPC518316
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E)-5,7-Dihydroxy-8-(4-hydroxy-3-methylbut-2-en-1-yl)-3-(4-hydroxyphenyl)-4H-chromen-4-one
IUPAC Name 5,7-dihydroxy-8-(4-hydroxy-3-methyl-but-2-enyl)-3-(4-hydroxyphenyl)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 MEADLGUPYQNUNF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O6/c1-11(9-21)2-7-14-16(23)8-17(24)18-19(25)15(10-26-20(14)18)12-3-5-13(22)6-4-12/h2-6,8,10,21-24H,7,9H2,1H3
SMILES CC(=CCC1=C(O)C=C(O)C2=C1OC=C(C1=CC=C(O)C=C1)C2=O)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.11 Volume:   357.82
?
Van der Waals volume.
Dense:   0.99 LogP:   2.034
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.075
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.577
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   111.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.536 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.845 Fsp3:   0.15
MCE-18:   19.0
?
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:   0.758 Fluc inhibitor:   0.573
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.973
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.586
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.215 Promiscuous compounds:   0.154

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.034 MDCK Permeability:   -4.808
Pgp-inhibitor:   0.009 Pgp-substrate:   0.456
PAMPA:   0.898
?
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):   0.015
20% Bioavailability (F20%):   0.622 30% Bioavailability (F30%):   0.866
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.021 MRP1:   0.565
Plasma Protein Binding (PPB):   94.452% Volume Distribution (VD):   0.234
Fu: 5.307%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.624
OATP1B3 inhibitor:   0.424 BCRP inhibitor:   0.893
BSEP inhibitor:   0.395

ADMET: Metabolism

CYP1A2-inhibitor:   0.193 CYP1A2-substrate:   0.936
CYP2C19-inhibitor:   0.017 CYP2C19-substrate:   0.777
CYP2C9-inhibitor:   0.991 CYP2C9-substrate:   0.949
CYP2D6-inhibitor:   0.915 CYP2D6-substrate:   0.547
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.114
?
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):  5.118 Half-life (T1/2):  1.37

ADMET: Toxicity

hERG Blockers:  0.086 hERG Blockers (10um):  0.535
Human Hepatotoxicity (H-HT):  0.536 Drug-induced Liver Injury (DILI):  0.748
AMES Toxicity:  0.652 Rat Oral Acute Toxicity:  0.692
Maximum Recommended Daily Dose:  0.643 Skin Sensitization:  0.771
Carcinogencity:  0.578 Eye Corrosion:  0.0
Eye Irritation:  0.869 Respiratory Toxicity:  0.917
Drug-induced Neurotoxicity:  0.227 Ototoxicity:  0.321
Hematotoxicity:  0.111 Drug-induced Nephrotoxicity:  0.166
Genotoxicity:  0.981 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.305 Hek293 Cytotoxicity:  0.69
BCF:   1.259
?
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:   3.955
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.071
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.584
?
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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s40502-015-0143-x]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1093/pcp/pcg054]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443709050069]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443711030101]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Leaves n.a. n.a. PMID[12713396]
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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota roots n.a. n.a. PMID[20022509]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21123068]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21866899]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22074222]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[22074222]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23325115]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Roots n.a. n.a. PMID[23541646]
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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28140583]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28522265]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[29641206]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[32196343]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[39683057]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[7381508]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7786 Lentinus tigrinus Species Lentinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10026 Mitracarpus scaber Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52079 Bolusanthus speciosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29384 Glycyrrhiza glabra 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]
NPO1698 Glycyrrhiza inflata 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[TCM_Taiwan]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7786 Lentinus tigrinus Species Lentinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10026 Mitracarpus scaber Species Rubiaceae 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 NPC518316 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
0.8621 High Similarity NPC144118
0.7302 Intermediate Similarity NPC38545
0.7188 Intermediate Similarity NPC222298
0.7188 Intermediate Similarity NPC604003
0.697 Remote Similarity NPC80962
0.6923 Remote Similarity NPC40868
0.6714 Remote Similarity NPC78103
0.6571 Remote Similarity NPC610891
0.6324 Remote Similarity NPC92075
0.6269 Remote Similarity NPC204985
0.6232 Remote Similarity NPC169162
0.6197 Remote Similarity NPC604255
0.6111 Remote Similarity NPC117836
0.6087 Remote Similarity NPC606794
0.5694 Remote Similarity NPC130589
0.5676 Remote Similarity NPC51887
0.5526 Remote Similarity NPC604254
0.55 Remote Similarity NPC349624
0.5467 Remote Similarity NPC219861
0.5455 Remote Similarity NPC177308
0.5429 Remote Similarity NPC259166
0.5278 Remote Similarity NPC171916
0.5205 Remote Similarity NPC213659
0.5205 Remote Similarity NPC326109
0.5195 Remote Similarity NPC323626
0.5195 Remote Similarity NPC611367
0.5156 Remote Similarity NPC39426
0.5143 Remote Similarity NPC9117
0.5143 Remote Similarity NPC220062
0.5128 Remote Similarity NPC31627
0.5075 Remote Similarity NPC295384
0.5065 Remote Similarity NPC237635
0.5063 Remote Similarity NPC327269
0.5059 Remote Similarity NPC324447

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC518316 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
0.5156 Remote Similarity NPD1510 Phase 2

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