Natural Product: NPC104406

Natural Product IDNPC104406
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isowighteone
IUPAC Name 3-(2,2-dimethylchromen-6-yl)-7-hydroxychromen-4-one
Synonyms Isowighteone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1271888
PubChem CID 5316097
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0003530] Pyranoisoflavonoids

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 PWAACAMQKVIVPZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H16O4/c1-20(2)8-7-13-9-12(3-6-17(13)24-20)16-11-23-18-10-14(21)4-5-15(18)19(16)22/h3-11,21H,1-2H3
SMILES CC1(C)C=Cc2cc(ccc2O1)c1coc2cc(ccc2c1=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   320.1 Volume:   331.683
?
Van der Waals volume.
Dense:   0.965 LogP:   3.32
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.034
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.952
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.724 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.666 Fsp3:   0.15
MCE-18:   48.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.914 Fluc inhibitor:   0.975
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.956
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.774
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.534 Promiscuous compounds:   0.223

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.787 MDCK Permeability:   -4.705
Pgp-inhibitor:   0.273 Pgp-substrate:   0.151
PAMPA:   0.241
?
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):   0.008
20% Bioavailability (F20%):   0.615 30% Bioavailability (F30%):   0.907
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.158 MRP1:   0.342
Plasma Protein Binding (PPB):   97.104% Volume Distribution (VD):   0.123
Fu: 2.273%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.747
OATP1B3 inhibitor:   0.853 BCRP inhibitor:   0.972
BSEP inhibitor:   0.956

ADMET: Metabolism

CYP1A2-inhibitor:   0.077 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.92
CYP2C9-inhibitor:   0.399 CYP2C9-substrate:   0.956
CYP2D6-inhibitor:   0.031 CYP2D6-substrate:   0.393
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.128 CYP2C8-inhibitor:   1.0
HLM stability:   0.439
?
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):  5.255 Half-life (T1/2):  0.803

ADMET: Toxicity

hERG Blockers:  0.297 hERG Blockers (10um):  0.597
Human Hepatotoxicity (H-HT):  0.538 Drug-induced Liver Injury (DILI):  0.634
AMES Toxicity:  0.722 Rat Oral Acute Toxicity:  0.728
Maximum Recommended Daily Dose:  0.842 Skin Sensitization:  0.197
Carcinogencity:  0.87 Eye Corrosion:  0.01
Eye Irritation:  0.946 Respiratory Toxicity:  0.88
Drug-induced Neurotoxicity:  0.52 Ototoxicity:  0.318
Hematotoxicity:  0.166 Drug-induced Nephrotoxicity:  0.234
Genotoxicity:  0.846 RPMI-8226 Immunitoxicity:  0.076
A549 Cytotoxicity:  0.149 Hek293 Cytotoxicity:  0.582
BCF:   1.621
?
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:   4.491
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.659
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.212
?
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
NPO32756 ulex europaeus ssp. europaeus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[11858751]
NPO29080 Ulex airensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[11858751]
NPO18089 Chlorophora tinctoria n.a. n.a. n.a. leaves and twigs n.a. n.a. PMID[12502337]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota Stems; Barks n.a. n.a. PMID[12828487]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[17517504]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota Barks n.a. n.a. PMID[18302333]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota seeds n.a. n.a. PMID[18359631]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. fruit n.a. PMID[20663508]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20934335]
NPO13906 Ficus mucuso Species Moraceae Eukaryota n.a. fruit n.a. PMID[21619045]
NPO13906 Ficus mucuso Species Moraceae Eukaryota figs Tongolo-Yaound, in the Central Region of Cameroon 2008-JUN PMID[21619045]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23022281]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24507928]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota Fruits n.a. n.a. PMID[25710081]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[3069958]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. seed n.a. PMID[8759164]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9544566]
NPO29080 Ulex airensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13906 Ficus mucuso Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18089 Chlorophora tinctoria n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18089 Chlorophora tinctoria n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO18089 Chlorophora tinctoria n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29080 Ulex airensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13906 Ficus mucuso Species Moraceae 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
NPT1333 Individual protein Enoyl-acyl-carrier protein reductase Plasmodium falciparum Inhibition = 66.9 % PMID[21619045]
NPT1333 Individual protein Enoyl-acyl-carrier protein reductase Plasmodium falciparum IC50 = 58950.0 nM PMID[21619045]
NPT493 Individual protein Neuraminidase Influenza A virus IC50 > 50.0 ug.mL-1 PMID[20934335]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20 Organism Candida albicans Candida albicans IC50 = 5.0 ug.mL-1 PMID[12502337]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans IC50 = 7.5 ug.mL-1 PMID[12502337]
NPT2 Others Unspecified n.a. IC50 > 50.0 ug.mL-1 PMID[12502337]
NPT2 Others Unspecified n.a. Inhibition = 92.7 % PMID[21619045]
NPT2 Others Unspecified n.a. IC50 = 17600.0 nM PMID[21619045]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 8.3 % PMID[35489224]





 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 NPC104406 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
0.7536 Intermediate Similarity NPC107838
0.7429 Intermediate Similarity NPC108859
0.7429 Intermediate Similarity NPC609101
0.7391 Intermediate Similarity NPC266572
0.6622 Remote Similarity NPC223701
0.6622 Remote Similarity NPC472583
0.6622 Remote Similarity NPC7989
0.6486 Remote Similarity NPC285623
0.6438 Remote Similarity NPC149875
0.6364 Remote Similarity NPC209560
0.6364 Remote Similarity NPC490700
0.6329 Remote Similarity NPC302762
0.6032 Remote Similarity NPC234560
0.6 Remote Similarity NPC474052
0.5972 Remote Similarity NPC600644
0.5942 Remote Similarity NPC12377
0.5857 Remote Similarity NPC80710
0.5714 Remote Similarity NPC231763
0.5694 Remote Similarity NPC35544
0.5676 Remote Similarity NPC215311
0.5676 Remote Similarity NPC488135
0.5652 Remote Similarity NPC203747
0.5634 Remote Similarity NPC139364
0.5606 Remote Similarity NPC242893
0.5513 Remote Similarity NPC74178
0.5467 Remote Similarity NPC97716
0.5429 Remote Similarity NPC609386
0.5316 Remote Similarity NPC134796
0.5224 Remote Similarity NPC212767
0.5211 Remote Similarity NPC181124
0.5205 Remote Similarity NPC12175
0.5205 Remote Similarity NPC195763
0.5205 Remote Similarity NPC191741
0.52 Remote Similarity NPC607923
0.5195 Remote Similarity NPC37208
0.519 Remote Similarity NPC51759
0.5143 Remote Similarity NPC487215
0.5135 Remote Similarity NPC200060
0.5135 Remote Similarity NPC55162
0.5128 Remote Similarity NPC611071
0.5122 Remote Similarity NPC484043
0.5068 Remote Similarity NPC262623
0.5065 Remote Similarity NPC24673
0.506 Remote Similarity NPC123653
0.5059 Remote Similarity NPC78071

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC104406 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