Natural Product: NPC159103

Natural Product IDNPC159103
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Quercetin-3',4'-Di-O-Methyl Ether
IUPAC Name 2-(3,4-dimethoxyphenyl)-3,5,7-trihydroxychromen-4-one
Synonyms 3',4'-O-dimethylquercetin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2043330
PubChem CID 5487855
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

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 MHALJYZRPGYQSI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O7/c1-22-11-4-3-8(5-12(11)23-2)17-16(21)15(20)14-10(19)6-9(18)7-13(14)24-17/h3-7,18-19,21H,1-2H3
SMILES COc1ccc(cc1OC)c1c(c(=O)c2c(cc(cc2o1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.07 Volume:   317.359
?
Van der Waals volume.
Dense:   1.04 LogP:   2.005
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.03
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.817
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   109.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.677 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.337 Fsp3:   0.118
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:   0.565 Fluc inhibitor:   0.808
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.885
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.687
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.413 Promiscuous compounds:   0.904

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.306 MDCK Permeability:   -4.841
Pgp-inhibitor:   0.966 Pgp-substrate:   0.158
PAMPA:   0.072
?
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):   0.349
20% Bioavailability (F20%):   0.019 30% Bioavailability (F30%):   0.657
50% Bioavailability (F50%):   0.966

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.583
Plasma Protein Binding (PPB):   98.094% Volume Distribution (VD):   -0.525
Fu: 1.317%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.951
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.983

ADMET: Metabolism

CYP1A2-inhibitor:   0.958 CYP1A2-substrate:   0.017
CYP2C19-inhibitor:   0.01 CYP2C19-substrate:   0.815
CYP2C9-inhibitor:   0.19 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.898
CYP3A4-inhibitor:   0.021 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.993
?
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):  4.963 Half-life (T1/2):  1.641

ADMET: Toxicity

hERG Blockers:  0.077 hERG Blockers (10um):  0.457
Human Hepatotoxicity (H-HT):  0.405 Drug-induced Liver Injury (DILI):  0.759
AMES Toxicity:  0.566 Rat Oral Acute Toxicity:  0.473
Maximum Recommended Daily Dose:  0.672 Skin Sensitization:  0.492
Carcinogencity:  0.745 Eye Corrosion:  0.709
Eye Irritation:  0.996 Respiratory Toxicity:  0.774
Drug-induced Neurotoxicity:  0.071 Ototoxicity:  0.099
Hematotoxicity:  0.133 Drug-induced Nephrotoxicity:  0.052
Genotoxicity:  0.832 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.18 Hek293 Cytotoxicity:  0.533
BCF:   0.985
?
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:   3.739
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.435
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.964
?
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
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. stem n.a. PMID[12575075]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. leaf n.a. PMID[12575075]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. whole plant n.a. PMID[15577255]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. heartwood n.a. PMID[19420770]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. heartwood n.a. PMID[21800859]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21800859]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[23127886]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23234407]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota seeds Nanning, Guangxi Province, China 2013-APR PMID[26398312]
NPO26395 Siegesbeckia pubescens Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[28009521]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[30188125]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26395 Siegesbeckia pubescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28940 Sigesbeckia glabrescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29463 Pogostemon cablin 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
NPT1628 Individual protein Thrombin Oryctolagus cuniculus TT = 9.9 s PMID[22647223]
NPT1628 Individual protein Thrombin Oryctolagus cuniculus PT = 5.8 s PMID[22647223]
NPT1628 Individual protein Thrombin Oryctolagus cuniculus APTT = 58.7 s PMID[22647223]
NPT1628 Individual protein Thrombin Oryctolagus cuniculus Activity = 6.6 g/L PMID[22647223]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus IC50 = 35000.0 nM PMID[23234407]
NPT35 Others n.a. n.a. IC50 = 85340.0 nM PMID[23234407]
NPT2535 Tissue Plasma Oryctolagus cuniculus TIME = 0.00275 hr PMID[34902735]
NPT2535 Tissue Plasma Oryctolagus cuniculus TIME = 0.01631 hr PMID[34902735]
NPT2535 Tissue Plasma Oryctolagus cuniculus TIME = 0.001611 hr PMID[34902735]

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 NPC159103 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
0.8077 Intermediate Similarity NPC241838
0.7885 Intermediate Similarity NPC219330
0.7778 Intermediate Similarity NPC54394
0.75 Intermediate Similarity NPC125062
0.7455 Intermediate Similarity NPC166753
0.7407 Intermediate Similarity NPC28274
0.7321 Intermediate Similarity NPC12200
0.7321 Intermediate Similarity NPC603596
0.7321 Intermediate Similarity NPC609179
0.7091 Intermediate Similarity NPC50403
0.6897 Remote Similarity NPC133953
0.6842 Remote Similarity NPC50728
0.6667 Remote Similarity NPC179271
0.6604 Remote Similarity NPC116775
0.6604 Remote Similarity NPC187432
0.6481 Remote Similarity NPC20791
0.6441 Remote Similarity NPC224137
0.6271 Remote Similarity NPC602344
0.6182 Remote Similarity NPC169749
0.6167 Remote Similarity NPC261548
0.5932 Remote Similarity NPC59951
0.5932 Remote Similarity NPC231772
0.5932 Remote Similarity NPC62536
0.5932 Remote Similarity NPC610359
0.5902 Remote Similarity NPC200316
0.5902 Remote Similarity NPC606638
0.5873 Remote Similarity NPC605634
0.5833 Remote Similarity NPC134677
0.5797 Remote Similarity NPC171821
0.5789 Remote Similarity NPC216361
0.5763 Remote Similarity NPC44079
0.5738 Remote Similarity NPC200740
0.5738 Remote Similarity NPC82325
0.569 Remote Similarity NPC256042
0.5672 Remote Similarity NPC183
0.5667 Remote Similarity NPC201451
0.5667 Remote Similarity NPC143799
0.5645 Remote Similarity NPC52005
0.5645 Remote Similarity NPC162351
0.5614 Remote Similarity NPC601197
0.5574 Remote Similarity NPC49824
0.5556 Remote Similarity NPC254306
0.5556 Remote Similarity NPC252933
0.55 Remote Similarity NPC184536
0.55 Remote Similarity NPC103342
0.55 Remote Similarity NPC152042
0.5484 Remote Similarity NPC115798
0.5484 Remote Similarity NPC255350
0.541 Remote Similarity NPC286342
0.541 Remote Similarity NPC87125
0.541 Remote Similarity NPC281207
0.541 Remote Similarity NPC120464
0.541 Remote Similarity NPC483773
0.5397 Remote Similarity NPC93376
0.5397 Remote Similarity NPC236769
0.5397 Remote Similarity NPC195202
0.5397 Remote Similarity NPC604422
0.5397 Remote Similarity NPC610401
0.5373 Remote Similarity NPC200694
0.5333 Remote Similarity NPC21100
0.5333 Remote Similarity NPC26227
0.5323 Remote Similarity NPC86485
0.5323 Remote Similarity NPC600900
0.5312 Remote Similarity NPC183950
0.5312 Remote Similarity NPC279989
0.5246 Remote Similarity NPC123886
0.5246 Remote Similarity NPC98661
0.5238 Remote Similarity NPC55205
0.5231 Remote Similarity NPC227192
0.5231 Remote Similarity NPC483775
0.5224 Remote Similarity NPC205046
0.5195 Remote Similarity NPC197285
0.5161 Remote Similarity NPC601901
0.5161 Remote Similarity NPC605755
0.5156 Remote Similarity NPC602125
0.5152 Remote Similarity NPC607815
0.5147 Remote Similarity NPC130955
0.5143 Remote Similarity NPC479305
0.5128 Remote Similarity NPC88023
0.5128 Remote Similarity NPC165970
0.5128 Remote Similarity NPC136761
0.5128 Remote Similarity NPC309025
0.5128 Remote Similarity NPC606270
0.5077 Remote Similarity NPC604021
0.5063 Remote Similarity NPC288131

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC159103 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
0.6481 Remote Similarity NPD1512 Phase 3
0.5484 Remote Similarity NPD2801 Pre-clinical

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