Natural Product: NPC525604

Natural Product IDNPC525604
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sayanedine
IUPAC Name 3-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-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 JSDXTLJPMLRQOB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O5/c1-20-11-4-5-12-15(8-11)22-9-13(17(12)19)10-3-6-14(18)16(7-10)21-2/h3-9,18H,1-2H3
SMILES COC1=CC=C2C(=O)C(C3=CC=C(O)C(OC)=C3)=COC2=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.08 Volume:   299.778
?
Van der Waals volume.
Dense:   0.994 LogP:   2.236
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.512
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.808
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.804 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.06 Fsp3:   0.118
MCE-18:   17.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.315 Fluc inhibitor:   0.997
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.971
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.547
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.482 Promiscuous compounds:   0.611

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.863 MDCK Permeability:   -4.692
Pgp-inhibitor:   0.267 Pgp-substrate:   0.045
PAMPA:   0.388
?
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):   0.373
20% Bioavailability (F20%):   0.257 30% Bioavailability (F30%):   0.551
50% Bioavailability (F50%):   0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.609
Plasma Protein Binding (PPB):   90.578% Volume Distribution (VD):   -0.247
Fu: 10.901%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.887
BSEP inhibitor:   0.876

ADMET: Metabolism

CYP1A2-inhibitor:   0.995 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.777 CYP2C19-substrate:   0.978
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.542
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.895
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.765
CYP2B6-substrate:   0.463 CYP2C8-inhibitor:   0.995
HLM stability:   0.737
?
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):  7.555 Half-life (T1/2):  0.959

ADMET: Toxicity

hERG Blockers:  0.228 hERG Blockers (10um):  0.566
Human Hepatotoxicity (H-HT):  0.485 Drug-induced Liver Injury (DILI):  0.807
AMES Toxicity:  0.657 Rat Oral Acute Toxicity:  0.493
Maximum Recommended Daily Dose:  0.656 Skin Sensitization:  0.269
Carcinogencity:  0.808 Eye Corrosion:  0.095
Eye Irritation:  0.963 Respiratory Toxicity:  0.801
Drug-induced Neurotoxicity:  0.497 Ototoxicity:  0.264
Hematotoxicity:  0.293 Drug-induced Nephrotoxicity:  0.407
Genotoxicity:  0.525 RPMI-8226 Immunitoxicity:  0.123
A549 Cytotoxicity:  0.211 Hek293 Cytotoxicity:  0.429
BCF:   1.044
?
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:   3.651
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.429
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.017
?
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
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jfca.2005.08.001]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[15286289]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18460139]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. seed n.a. PMID[20947202]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24253552]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[8987503]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Wax n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Tissue Culture n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Sprout Seedling n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Seeds n.a. Database[Phenol-Explorer]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11043 Pisum sativum 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 NPC525604 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
0.7818 Intermediate Similarity NPC181124
0.7414 Intermediate Similarity NPC139364
0.7143 Intermediate Similarity NPC185607
0.7 Intermediate Similarity NPC114192
0.6909 Remote Similarity NPC182428
0.6557 Remote Similarity NPC602183
0.623 Remote Similarity NPC471590
0.619 Remote Similarity NPC254702
0.619 Remote Similarity NPC109187
0.6167 Remote Similarity NPC216314
0.6167 Remote Similarity NPC603503
0.6066 Remote Similarity NPC136095
0.6056 Remote Similarity NPC605730
0.6024 Remote Similarity NPC231194
0.5873 Remote Similarity NPC12377
0.5821 Remote Similarity NPC185401
0.5806 Remote Similarity NPC100971
0.5806 Remote Similarity NPC203747
0.5806 Remote Similarity NPC121522
0.5806 Remote Similarity NPC209560
0.5806 Remote Similarity NPC490700
0.5781 Remote Similarity NPC80710
0.5738 Remote Similarity NPC605229
0.5645 Remote Similarity NPC479067
0.5606 Remote Similarity NPC254741
0.5556 Remote Similarity NPC609386
0.5469 Remote Similarity NPC181209
0.5455 Remote Similarity NPC153008
0.5441 Remote Similarity NPC260640
0.541 Remote Similarity NPC195919
0.5397 Remote Similarity NPC333691
0.5385 Remote Similarity NPC229729
0.5373 Remote Similarity NPC478213
0.5333 Remote Similarity NPC211014
0.5312 Remote Similarity NPC162680
0.5312 Remote Similarity NPC69430
0.5312 Remote Similarity NPC303644
0.5303 Remote Similarity NPC191741
0.5263 Remote Similarity NPC161749
0.525 Remote Similarity NPC479407
0.5246 Remote Similarity NPC120924
0.5224 Remote Similarity NPC134726
0.5156 Remote Similarity NPC10467
0.5156 Remote Similarity NPC116632
0.5152 Remote Similarity NPC139293
0.5152 Remote Similarity NPC264289
0.5147 Remote Similarity NPC35544
0.5077 Remote Similarity NPC216769
0.5077 Remote Similarity NPC124714
0.5077 Remote Similarity NPC610981
0.5075 Remote Similarity NPC12175
0.5075 Remote Similarity NPC40290
0.5075 Remote Similarity NPC100263
0.5075 Remote Similarity NPC195763
0.5062 Remote Similarity NPC48773

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC525604 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
0.5645 Remote Similarity NPD2796 Phase 2
0.5263 Remote Similarity NPD4381 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