Natural Product: NPC162351

Natural Product IDNPC162351
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Myricetin 3,3',4'-Trimethylether
IUPAC Name 5,7-dihydroxy-2-(3-hydroxy-4,5-dimethoxyphenyl)-3-methoxychromen-4-one
Synonyms Myricetin 3,3',4'-Trimethylether
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1689269
PubChem CID 44259719
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002596] 4'-O-methylated flavonoids

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 YTYFGDJADQYGLC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O8/c1-23-13-5-8(4-11(21)17(13)24-2)16-18(25-3)15(22)14-10(20)6-9(19)7-12(14)26-16/h4-7,19-21H,1-3H3
SMILES COc1c(O)cc(cc1OC)c1oc2cc(O)cc(c2c(=O)c1OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.08 Volume:   343.445
?
Van der Waals volume.
Dense:   1.048 LogP:   2.155
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.075
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.152
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   118.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.65 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.582 Fsp3:   0.167
MCE-18:   20.0
?
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:   0.349 Fluc inhibitor:   0.298
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.89
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.68
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.363 Promiscuous compounds:   0.833

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.174 MDCK Permeability:   -4.801
Pgp-inhibitor:   0.444 Pgp-substrate:   0.389
PAMPA:   0.235
?
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):   0.033
20% Bioavailability (F20%):   0.045 30% Bioavailability (F30%):   0.473
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.013 MRP1:   0.828
Plasma Protein Binding (PPB):   97.345% Volume Distribution (VD):   -0.647
Fu: 2.138%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.289
OATP1B3 inhibitor:   0.973 BCRP inhibitor:   0.989
BSEP inhibitor:   0.923

ADMET: Metabolism

CYP1A2-inhibitor:   0.989 CYP1A2-substrate:   0.129
CYP2C19-inhibitor:   0.012 CYP2C19-substrate:   0.558
CYP2C9-inhibitor:   0.448 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.005
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.986
?
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):  4.212 Half-life (T1/2):  1.283

ADMET: Toxicity

hERG Blockers:  0.064 hERG Blockers (10um):  0.487
Human Hepatotoxicity (H-HT):  0.425 Drug-induced Liver Injury (DILI):  0.658
AMES Toxicity:  0.467 Rat Oral Acute Toxicity:  0.434
Maximum Recommended Daily Dose:  0.684 Skin Sensitization:  0.622
Carcinogencity:  0.712 Eye Corrosion:  0.518
Eye Irritation:  0.992 Respiratory Toxicity:  0.759
Drug-induced Neurotoxicity:  0.093 Ototoxicity:  0.123
Hematotoxicity:  0.135 Drug-induced Nephrotoxicity:  0.065
Genotoxicity:  0.851 RPMI-8226 Immunitoxicity:  0.091
A549 Cytotoxicity:  0.268 Hek293 Cytotoxicity:  0.596
BCF:   1.047
?
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:   3.481
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.541
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.796
?
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
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota n.a. n.a. n.a. PMID[10650080]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota seeds n.a. n.a. PMID[10785422]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota Seeds n.a. n.a. PMID[11277757]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota n.a. leaf n.a. PMID[21265555]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota leaves Khon Kaen, Thailand 2006-AUG PMID[21265555]
NPO32817 gardenia oudiepe Species Rubiaceae Eukaryota flowering buds and leaf bases Foret Plate, New Caledonia n.a. PMID[25659770]
NPO32817 gardenia oudiepe Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[29207340]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota n.a. n.a. n.a. PMID[9934464]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT1310 Individual protein Xanthine dehydrogenase Bos taurus IC50 = 90.0 nM PMID[29207340]
NPT1310 Individual protein Xanthine dehydrogenase Bos taurus Ratio IC50 = 3.0 n.a. PMID[29207340]
NPT3892 Individual protein Tumor necrosis factor receptor superfamily member 10B Homo sapiens FC = 2.2 n.a. PMID[21265555]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT165 Cell line HeLa Homo sapiens IC50 = 8100.0 nM PMID[31784199]
NPT83 Cell line MCF7 Homo sapiens IC50 = 10300.0 nM PMID[31784199]

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 NPC162351 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
0.7925 Intermediate Similarity NPC610359
0.7736 Intermediate Similarity NPC123886
0.7636 Intermediate Similarity NPC29841
0.75 Intermediate Similarity NPC603596
0.75 Intermediate Similarity NPC606638
0.75 Intermediate Similarity NPC609179
0.7321 Intermediate Similarity NPC82325
0.7193 Intermediate Similarity NPC206604
0.7091 Intermediate Similarity NPC184536
0.7091 Intermediate Similarity NPC103342
0.7069 Intermediate Similarity NPC279989
0.6964 Remote Similarity NPC286342
0.6964 Remote Similarity NPC59951
0.661 Remote Similarity NPC235215
0.6452 Remote Similarity NPC158874
0.6333 Remote Similarity NPC78302
0.6102 Remote Similarity NPC50403
0.6102 Remote Similarity NPC62536
0.6102 Remote Similarity NPC601901
0.6061 Remote Similarity NPC97255
0.6034 Remote Similarity NPC472438
0.5932 Remote Similarity NPC219330
0.5902 Remote Similarity NPC54394
0.5882 Remote Similarity NPC470458
0.5882 Remote Similarity NPC269285
0.5821 Remote Similarity NPC259632
0.5806 Remote Similarity NPC52005
0.5806 Remote Similarity NPC12200
0.5714 Remote Similarity NPC481044
0.5645 Remote Similarity NPC115798
0.5645 Remote Similarity NPC159103
0.5574 Remote Similarity NPC28274
0.5574 Remote Similarity NPC76376
0.5574 Remote Similarity NPC120464
0.5574 Remote Similarity NPC483773
0.5507 Remote Similarity NPC56786
0.55 Remote Similarity NPC607530
0.5484 Remote Similarity NPC9609
0.5469 Remote Similarity NPC183950
0.5469 Remote Similarity NPC133953
0.5469 Remote Similarity NPC125062
0.541 Remote Similarity NPC266960
0.5405 Remote Similarity NPC470460
0.5405 Remote Similarity NPC265530
0.5325 Remote Similarity NPC609478
0.5323 Remote Similarity NPC231772
0.5323 Remote Similarity NPC241838
0.5323 Remote Similarity NPC163524
0.5312 Remote Similarity NPC25495
0.5312 Remote Similarity NPC177298
0.5312 Remote Similarity NPC236769
0.5312 Remote Similarity NPC474520
0.527 Remote Similarity NPC470461
0.5238 Remote Similarity NPC600900
0.5195 Remote Similarity NPC219904
0.5161 Remote Similarity NPC203891
0.5156 Remote Similarity NPC176300
0.5156 Remote Similarity NPC270620
0.5128 Remote Similarity NPC120099
0.5079 Remote Similarity NPC214138
0.5079 Remote Similarity NPC176665
0.5079 Remote Similarity NPC146679
0.5079 Remote Similarity NPC101830
0.5077 Remote Similarity NPC58382
0.5075 Remote Similarity NPC605634
0.5065 Remote Similarity NPC325555
0.5065 Remote Similarity NPC226304
0.5063 Remote Similarity NPC223747
0.5063 Remote Similarity NPC209023

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC162351 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