Natural Product: NPC524391

Natural Product IDNPC524391
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R})-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-8-(3-methylbut-2-enyl)chroman-4-one
IUPAC Name (2~{R})-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-8-(3-methylbut-2-enyl)chroman-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated flavanones

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 XJUDJFVOICLOMY-GOSISDBHSA-N
Standard InCHI InChI=1S/C20H20O6/c1-10(2)3-5-12-14(22)8-16(24)19-17(25)9-18(26-20(12)19)11-4-6-13(21)15(23)7-11/h3-4,6-8,18,21-24H,5,9H2,1-2H3/t18-/m1/s1
SMILES CC(C)=CCC1=C(O)C=C(O)C2=C1O[C@@H](C1=CC=C(O)C(O)=C1)CC2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.13 Volume:   360.456
?
Van der Waals volume.
Dense:   0.988 LogP:   3.559
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.218
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.77
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   107.22
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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:   0.493 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.347 Fsp3:   0.25
MCE-18:   63.2
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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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.845 Fluc inhibitor:   0.708
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.654
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.492
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.383 Promiscuous compounds:   0.156

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.057 MDCK Permeability:   -4.776
Pgp-inhibitor:   0.86 Pgp-substrate:   0.014
PAMPA:   0.187
?
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):   0.071
20% Bioavailability (F20%):   0.893 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.929
Plasma Protein Binding (PPB):   96.012% Volume Distribution (VD):   0.063
Fu: 3.567%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.442

ADMET: Metabolism

CYP1A2-inhibitor:   0.022 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.965 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.031 CYP2C9-substrate:   0.014
CYP2D6-inhibitor:   0.176 CYP2D6-substrate:   0.987
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):  9.592 Half-life (T1/2):  1.677

ADMET: Toxicity

hERG Blockers:  0.041 hERG Blockers (10um):  0.577
Human Hepatotoxicity (H-HT):  0.679 Drug-induced Liver Injury (DILI):  0.451
AMES Toxicity:  0.828 Rat Oral Acute Toxicity:  0.778
Maximum Recommended Daily Dose:  0.583 Skin Sensitization:  0.988
Carcinogencity:  0.382 Eye Corrosion:  0.001
Eye Irritation:  0.973 Respiratory Toxicity:  0.665
Drug-induced Neurotoxicity:  0.24 Ototoxicity:  0.649
Hematotoxicity:  0.096 Drug-induced Nephrotoxicity:  0.567
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.065
A549 Cytotoxicity:  0.839 Hek293 Cytotoxicity:  0.6
BCF:   1.761
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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:   4.695
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.057
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.455
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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
NPO54628 Wyethia spp. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45889 Encelia spp. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21100 Flourensia fiebrigii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21100 Flourensia fiebrigii Species Asteraceae 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 NPC524391 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
0.8364 Intermediate Similarity NPC107572
0.8364 Intermediate Similarity NPC32739
0.807 Intermediate Similarity NPC66515
0.7857 Intermediate Similarity NPC76372
0.7857 Intermediate Similarity NPC37496
0.7797 Intermediate Similarity NPC291878
0.7586 Intermediate Similarity NPC148757
0.7458 Intermediate Similarity NPC480990
0.7458 Intermediate Similarity NPC610133
0.7414 Intermediate Similarity NPC324436
0.7414 Intermediate Similarity NPC78
0.7414 Intermediate Similarity NPC306829
0.7097 Intermediate Similarity NPC161506
0.7031 Intermediate Similarity NPC166934
0.6825 Remote Similarity NPC36217
0.6667 Remote Similarity NPC182852
0.6615 Remote Similarity NPC24136
0.6515 Remote Similarity NPC300988
0.6418 Remote Similarity NPC484416
0.6406 Remote Similarity NPC485610
0.6308 Remote Similarity NPC10990
0.619 Remote Similarity NPC265040
0.6154 Remote Similarity NPC608140
0.6129 Remote Similarity NPC164980
0.6129 Remote Similarity NPC480991
0.6032 Remote Similarity NPC150408
0.6027 Remote Similarity NPC484417
0.5938 Remote Similarity NPC187282
0.5846 Remote Similarity NPC220998
0.5833 Remote Similarity NPC321011
0.5833 Remote Similarity NPC294852
0.5833 Remote Similarity NPC188679
0.5781 Remote Similarity NPC236766
0.5758 Remote Similarity NPC285555
0.5758 Remote Similarity NPC76338
0.5758 Remote Similarity NPC250242
0.5735 Remote Similarity NPC473078
0.5692 Remote Similarity NPC149026
0.5692 Remote Similarity NPC262038
0.5692 Remote Similarity NPC319910
0.5692 Remote Similarity NPC250214
0.5676 Remote Similarity NPC218226
0.5672 Remote Similarity NPC278476
0.5606 Remote Similarity NPC109223
0.5606 Remote Similarity NPC197252
0.5606 Remote Similarity NPC10937
0.5593 Remote Similarity NPC603284
0.5588 Remote Similarity NPC485620
0.5574 Remote Similarity NPC192083
0.5556 Remote Similarity NPC224851
0.5538 Remote Similarity NPC91560
0.5522 Remote Similarity NPC106976
0.5455 Remote Similarity NPC28918
0.5455 Remote Similarity NPC69674
0.5455 Remote Similarity NPC75049
0.5429 Remote Similarity NPC81697
0.5429 Remote Similarity NPC278249
0.5429 Remote Similarity NPC223812
0.5429 Remote Similarity NPC485615
0.5417 Remote Similarity NPC213896
0.5352 Remote Similarity NPC246948
0.5342 Remote Similarity NPC477958
0.5294 Remote Similarity NPC480158
0.5286 Remote Similarity NPC85162
0.5211 Remote Similarity NPC36275
0.5205 Remote Similarity NPC485617
0.52 Remote Similarity NPC192686
0.5167 Remote Similarity NPC213322
0.5156 Remote Similarity NPC246648
0.5152 Remote Similarity NPC258630
0.5147 Remote Similarity NPC17170
0.5135 Remote Similarity NPC214774
0.5135 Remote Similarity NPC479215
0.5082 Remote Similarity NPC482121
0.5082 Remote Similarity NPC270964
0.5072 Remote Similarity NPC125855
0.507 Remote Similarity NPC470890
0.5068 Remote Similarity NPC474021
0.5068 Remote Similarity NPC328164
0.5067 Remote Similarity NPC261063

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC524391 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
0.5574 Remote Similarity NPD2393 Clinical (unspecified phase)

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