Natural Product: NPC326109

Natural Product IDNPC326109
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isowighteone Hydrate
IUPAC Name 5,7-dihydroxy-3-[4-hydroxy-3-(3-methylbut-2-enyl)phenyl]chromen-4-one;hydrate
Synonyms Isowighteone Hydrate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1812593
PubChem CID 56676507
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002901] Isoflav-2-enes
          • [CHEMONTID:0000494] Isoflavones

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 WFALQMZTKNBBMO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O5.H2O/c1-11(2)3-4-13-7-12(5-6-16(13)22)15-10-25-18-9-14(21)8-17(23)19(18)20(15)24;/h3,5-10,21-23H,4H2,1-2H3;1H2
SMILES CC(=CCC1=C(C=CC(=C1)C2=COC3=CC(=CC(=C3C2=O)O)O)O)C.O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.12 Volume:   349.03
?
Van der Waals volume.
Dense:   0.969 LogP:   3.486
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.925
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.377
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   90.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.626 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.7 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:   0.813 Fluc inhibitor:   0.723
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.963
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.588
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.417 Promiscuous compounds:   0.068

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.98 MDCK Permeability:   -4.822
Pgp-inhibitor:   0.005 Pgp-substrate:   0.153
PAMPA:   0.863
?
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):   0.107
20% Bioavailability (F20%):   0.996 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.469
Plasma Protein Binding (PPB):   95.145% Volume Distribution (VD):   0.249
Fu: 4.294%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.333
OATP1B3 inhibitor:   0.827 BCRP inhibitor:   0.997
BSEP inhibitor:   0.137

ADMET: Metabolism

CYP1A2-inhibitor:   0.473 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.584 CYP2C19-substrate:   0.995
CYP2C9-inhibitor:   0.312 CYP2C9-substrate:   0.989
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.931
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):  6.557 Half-life (T1/2):  1.075

ADMET: Toxicity

hERG Blockers:  0.114 hERG Blockers (10um):  0.575
Human Hepatotoxicity (H-HT):  0.578 Drug-induced Liver Injury (DILI):  0.87
AMES Toxicity:  0.695 Rat Oral Acute Toxicity:  0.775
Maximum Recommended Daily Dose:  0.838 Skin Sensitization:  0.814
Carcinogencity:  0.612 Eye Corrosion:  0.001
Eye Irritation:  0.934 Respiratory Toxicity:  0.922
Drug-induced Neurotoxicity:  0.306 Ototoxicity:  0.342
Hematotoxicity:  0.1 Drug-induced Nephrotoxicity:  0.436
Genotoxicity:  0.99 RPMI-8226 Immunitoxicity:  0.079
A549 Cytotoxicity:  0.493 Hek293 Cytotoxicity:  0.73
BCF:   1.72
?
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:   4.609
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.722
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.254
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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
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]
NPO13906 Ficus mucuso Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
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 = 51.1 % PMID[21619045]
NPT1333 Individual protein Enoyl-acyl-carrier protein reductase Plasmodium falciparum IC50 = 248300.0 nM PMID[21619045]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Inhibition = 89.6 % PMID[21619045]
NPT2 Others Unspecified n.a. IC50 = 15620.0 nM PMID[21619045]

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 NPC326109 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
1.0 High Similarity NPC213659
0.7778 Intermediate Similarity NPC475705
0.7639 Intermediate Similarity NPC324447
0.7619 Intermediate Similarity NPC48624
0.7581 Intermediate Similarity NPC238279
0.746 Intermediate Similarity NPC215311
0.7344 Intermediate Similarity NPC80962
0.7188 Intermediate Similarity NPC232947
0.697 Remote Similarity NPC233918
0.6875 Remote Similarity NPC93552
0.6667 Remote Similarity NPC85131
0.6552 Remote Similarity NPC39426
0.6471 Remote Similarity NPC268059
0.6377 Remote Similarity NPC128774
0.6333 Remote Similarity NPC38065
0.6301 Remote Similarity NPC123653
0.6212 Remote Similarity NPC259166
0.6176 Remote Similarity NPC172250
0.6 Remote Similarity NPC608554
0.597 Remote Similarity NPC144118
0.5942 Remote Similarity NPC203077
0.5942 Remote Similarity NPC301217
0.5942 Remote Similarity NPC200694
0.5915 Remote Similarity NPC485109
0.5882 Remote Similarity NPC20472
0.5833 Remote Similarity NPC269285
0.5833 Remote Similarity NPC193792
0.5823 Remote Similarity NPC90497
0.5821 Remote Similarity NPC254702
0.5753 Remote Similarity NPC303197
0.5692 Remote Similarity NPC294409
0.5692 Remote Similarity NPC490701
0.5652 Remote Similarity NPC38545
0.5634 Remote Similarity NPC169162
0.5556 Remote Similarity NPC87545
0.5542 Remote Similarity NPC121647
0.5541 Remote Similarity NPC107838
0.5538 Remote Similarity NPC78341
0.5522 Remote Similarity NPC309154
0.5522 Remote Similarity NPC200316
0.5513 Remote Similarity NPC303174
0.5493 Remote Similarity NPC268204
0.5479 Remote Similarity NPC479305
0.5467 Remote Similarity NPC469404
0.5441 Remote Similarity NPC194653
0.5429 Remote Similarity NPC55832
0.5417 Remote Similarity NPC219917
0.5417 Remote Similarity NPC606200
0.5405 Remote Similarity NPC149875
0.5405 Remote Similarity NPC474052
0.5362 Remote Similarity NPC476055
0.5352 Remote Similarity NPC608523
0.5333 Remote Similarity NPC482075
0.5286 Remote Similarity NPC104728
0.527 Remote Similarity NPC166036
0.5263 Remote Similarity NPC52889
0.5217 Remote Similarity NPC481044
0.5205 Remote Similarity NPC40942
0.52 Remote Similarity NPC253822
0.5195 Remote Similarity NPC474960
0.5147 Remote Similarity NPC239363
0.5143 Remote Similarity NPC483637
0.5143 Remote Similarity NPC264550
0.5139 Remote Similarity NPC40868
0.5139 Remote Similarity NPC161124
0.5132 Remote Similarity NPC231763
0.5132 Remote Similarity NPC74178
0.5132 Remote Similarity NPC610891
0.5068 Remote Similarity NPC92075

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC326109 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
0.6552 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