Natural Product: NPC48479

Natural Product IDNPC48479
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7,3',5'-Tri-O-Methyltricetin
IUPAC Name 5-hydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-7-methoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL470242
PubChem CID 15222911
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-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 VIKKUMIXGIDYKY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O7/c1-22-10-6-11(19)17-12(20)8-13(25-14(17)7-10)9-4-15(23-2)18(21)16(5-9)24-3/h4-8,19,21H,1-3H3
SMILES COc1cc(c2c(=O)cc(c3cc(c(c(c3)OC)O)OC)oc2c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.09 Volume:   334.655
?
Van der Waals volume.
Dense:   1.028 LogP:   2.593
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.496
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.583
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   98.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.751 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.36 Fsp3:   0.167
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.324 Fluc inhibitor:   0.596
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.882
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.669
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.397 Promiscuous compounds:   0.687

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.165 MDCK Permeability:   -4.775
Pgp-inhibitor:   0.964 Pgp-substrate:   0.087
PAMPA:   0.004
?
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):   0.146
20% Bioavailability (F20%):   0.044 30% Bioavailability (F30%):   0.185
50% Bioavailability (F50%):   0.966

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.873
Plasma Protein Binding (PPB):   93.822% Volume Distribution (VD):   -0.484
Fu: 6.206%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.979

ADMET: Metabolism

CYP1A2-inhibitor:   0.978 CYP1A2-substrate:   0.979
CYP2C19-inhibitor:   0.875 CYP2C19-substrate:   0.43
CYP2C9-inhibitor:   0.987 CYP2C9-substrate:   0.689
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.991
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.01
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.922
HLM stability:   0.94
?
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):  5.566 Half-life (T1/2):  1.251

ADMET: Toxicity

hERG Blockers:  0.092 hERG Blockers (10um):  0.484
Human Hepatotoxicity (H-HT):  0.401 Drug-induced Liver Injury (DILI):  0.866
AMES Toxicity:  0.575 Rat Oral Acute Toxicity:  0.46
Maximum Recommended Daily Dose:  0.644 Skin Sensitization:  0.393
Carcinogencity:  0.808 Eye Corrosion:  0.431
Eye Irritation:  0.988 Respiratory Toxicity:  0.823
Drug-induced Neurotoxicity:  0.107 Ototoxicity:  0.116
Hematotoxicity:  0.235 Drug-induced Nephrotoxicity:  0.1
Genotoxicity:  0.479 RPMI-8226 Immunitoxicity:  0.11
A549 Cytotoxicity:  0.23 Hek293 Cytotoxicity:  0.488
BCF:   1.039
?
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:   3.662
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.276
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.812
?
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
NPO33004 lethedon tannaensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[10075750]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. stem n.a. PMID[21469695]
NPO19192 Sinocalamus affinis Species n.a. n.a. skin-removed stems Pingle Town, Sichuang Province, China 2008-AUG PMID[21469695]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. n.a. n.a. PMID[22690646]
NPO33004 lethedon tannaensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[8759170]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO25396 Betonica officinalis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25396 Betonica officinalis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO25396 Betonica officinalis Species Lamiaceae 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
NPT91 Cell line KB Homo sapiens IC50 = 7.7 ug.mL-1 PMID[8759170]

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 NPC48479 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
0.8039 Intermediate Similarity NPC33265
0.7778 Intermediate Similarity NPC137062
0.75 Intermediate Similarity NPC127447
0.75 Intermediate Similarity NPC29353
0.7358 Intermediate Similarity NPC234133
0.7273 Intermediate Similarity NPC177298
0.7273 Intermediate Similarity NPC195202
0.7273 Intermediate Similarity NPC223579
0.7222 Intermediate Similarity NPC108406
0.7037 Intermediate Similarity NPC120464
0.7037 Intermediate Similarity NPC276409
0.6786 Remote Similarity NPC328119
0.6667 Remote Similarity NPC124784
0.6545 Remote Similarity NPC284552
0.6102 Remote Similarity NPC58382
0.5965 Remote Similarity NPC483774
0.5862 Remote Similarity NPC483773
0.5821 Remote Similarity NPC248739
0.5789 Remote Similarity NPC75279
0.5738 Remote Similarity NPC252933
0.5738 Remote Similarity NPC78326
0.5735 Remote Similarity NPC603508
0.5652 Remote Similarity NPC158027
0.5652 Remote Similarity NPC600396
0.5634 Remote Similarity NPC18699
0.5625 Remote Similarity NPC602829
0.5593 Remote Similarity NPC57030
0.5593 Remote Similarity NPC62536
0.5593 Remote Similarity NPC76376
0.5574 Remote Similarity NPC206604
0.5571 Remote Similarity NPC159707
0.5571 Remote Similarity NPC14606
0.5571 Remote Similarity NPC194593
0.5493 Remote Similarity NPC121649
0.5484 Remote Similarity NPC183950
0.5484 Remote Similarity NPC47781
0.5467 Remote Similarity NPC311830
0.5424 Remote Similarity NPC275722
0.5424 Remote Similarity NPC103904
0.5424 Remote Similarity NPC262094
0.5424 Remote Similarity NPC152042
0.5417 Remote Similarity NPC205026
0.541 Remote Similarity NPC200740
0.541 Remote Similarity NPC270620
0.541 Remote Similarity NPC166753
0.5405 Remote Similarity NPC55443
0.5362 Remote Similarity NPC604322
0.5342 Remote Similarity NPC265624
0.5333 Remote Similarity NPC231772
0.5333 Remote Similarity NPC87125
0.5333 Remote Similarity NPC198826
0.5333 Remote Similarity NPC143799
0.5333 Remote Similarity NPC145379
0.5333 Remote Similarity NPC146679
0.5333 Remote Similarity NPC188871
0.5333 Remote Similarity NPC605755
0.5323 Remote Similarity NPC55619
0.5323 Remote Similarity NPC236769
0.5323 Remote Similarity NPC283600
0.5263 Remote Similarity NPC607707
0.5246 Remote Similarity NPC100916
0.5246 Remote Similarity NPC162313
0.5246 Remote Similarity NPC603662
0.5205 Remote Similarity NPC95090
0.5205 Remote Similarity NPC27408
0.5179 Remote Similarity NPC31872
0.5167 Remote Similarity NPC52611
0.5167 Remote Similarity NPC187498
0.5167 Remote Similarity NPC239128
0.5161 Remote Similarity NPC69394
0.5161 Remote Similarity NPC246204
0.5161 Remote Similarity NPC212678
0.5161 Remote Similarity NPC83508
0.5161 Remote Similarity NPC200388
0.5135 Remote Similarity NPC181712
0.5132 Remote Similarity NPC22832
0.5132 Remote Similarity NPC243930
0.5132 Remote Similarity NPC601144
0.5132 Remote Similarity NPC608742
0.5082 Remote Similarity NPC18260
0.5082 Remote Similarity NPC22519
0.5082 Remote Similarity NPC28274
0.5082 Remote Similarity NPC120163
0.5082 Remote Similarity NPC601901
0.5079 Remote Similarity NPC160951
0.5079 Remote Similarity NPC52005
0.5079 Remote Similarity NPC12200
0.5079 Remote Similarity NPC606638
0.5077 Remote Similarity NPC485299

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC48479 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