Natural Product: NPC274717

Natural Product IDNPC274717
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2R)-2',4'-Dihydroxy-7-Methoxy-8-Hydroxyethylflavan
IUPAC Name 4-[(2R)-8-(2-hydroxyethyl)-7-methoxy-3,4-dihydro-2H-chromen-2-yl]benzene-1,3-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1951301
PubChem CID 53468592
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 BJVDGVPUXJNXHR-QGZVFWFLSA-N
Standard InCHI InChI=1S/C18H20O5/c1-22-16-6-2-11-3-7-17(23-18(11)14(16)8-9-19)13-5-4-12(20)10-15(13)21/h2,4-6,10,17,19-21H,3,7-9H2,1H3/t17-/m1/s1
SMILES COc1ccc2CC[C@H](c3ccc(cc3O)O)Oc2c1CCO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.13 Volume:   322.347
?
Van der Waals volume.
Dense:   0.981 LogP:   2.29
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.364
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.205
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   17.0
TPSA:   79.15
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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:   0.808 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.037 Fsp3:   0.333
MCE-18:   55.25
?
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:   0.419 Fluc inhibitor:   0.759
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.085
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.208
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.159 Promiscuous compounds:   0.163

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.019 MDCK Permeability:   -4.792
Pgp-inhibitor:   0.306 Pgp-substrate:   0.352
PAMPA:   0.213
?
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):   0.0
20% Bioavailability (F20%):   0.01 30% Bioavailability (F30%):   0.257
50% Bioavailability (F50%):   0.663

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.036 MRP1:   0.799
Plasma Protein Binding (PPB):   93.16% Volume Distribution (VD):   0.099
Fu: 7.746%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.578
OATP1B3 inhibitor:   0.712 BCRP inhibitor:   0.933
BSEP inhibitor:   0.954

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.527 CYP2C19-substrate:   0.2
CYP2C9-inhibitor:   0.944 CYP2C9-substrate:   0.101
CYP2D6-inhibitor:   0.987 CYP2D6-substrate:   0.697
CYP3A4-inhibitor:   0.807 CYP3A4-substrate:   0.705
CYP2B6-substrate:   0.016 CYP2C8-inhibitor:   0.989
HLM stability:   0.924
?
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):  4.808 Half-life (T1/2):  1.996

ADMET: Toxicity

hERG Blockers:  0.259 hERG Blockers (10um):  0.476
Human Hepatotoxicity (H-HT):  0.846 Drug-induced Liver Injury (DILI):  0.025
AMES Toxicity:  0.542 Rat Oral Acute Toxicity:  0.352
Maximum Recommended Daily Dose:  0.752 Skin Sensitization:  0.904
Carcinogencity:  0.404 Eye Corrosion:  0.002
Eye Irritation:  0.92 Respiratory Toxicity:  0.305
Drug-induced Neurotoxicity:  0.266 Ototoxicity:  0.475
Hematotoxicity:  0.102 Drug-induced Nephrotoxicity:  0.438
Genotoxicity:  0.615 RPMI-8226 Immunitoxicity:  0.101
A549 Cytotoxicity:  0.352 Hek293 Cytotoxicity:  0.752
BCF:   1.097
?
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:   3.808
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.321
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.623
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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
NPO1524 Rosa rugosa Species Rosaceae Eukaryota Flowers n.a. n.a. DOI[10.1016/j.foodcont.2014.02.001]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota Flowers n.a. n.a. PMID[20467822]
NPO5877 Morus yunnanensis Species Moraceae Eukaryota n.a. n.a. n.a. PMID[22165973]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota flower buds n.a. n.a. PMID[24063567]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota Roots n.a. n.a. PMID[24461297]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[34332066]
NPO21070 Dendrosicyos socotrana Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5877 Morus yunnanensis Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19617 Crateva religiosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19617 Crateva religiosa Species Capparaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19617 Crateva religiosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19771 Pterocephalus plumosus Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21070 Dendrosicyos socotrana Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5877 Morus yunnanensis Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20337 Ageratina pichinchensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22808 Hesperocyparis stephensonii Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1524 Rosa rugosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21676 Heracleum pastinacifolium Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18059 Acacia orites 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
NPT43 Individual protein Tyrosinase Agaricus bisporus IC50 = 120.0 nM PMID[22165973]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens IC50 > 10000.0 nM PMID[24063567]
NPT306 Cell line PC-3 Homo sapiens IC50 > 10000.0 nM PMID[24063567]
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[24063567]
NPT2678 Cell line NB-4 Homo sapiens IC50 > 10000.0 nM PMID[24063567]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[24063567]

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 NPC274717 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
0.75 Intermediate Similarity NPC276212
0.5484 Remote Similarity NPC103420
0.5443 Remote Similarity NPC470308
0.5443 Remote Similarity NPC470307
0.5424 Remote Similarity NPC134195
0.5385 Remote Similarity NPC102540

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC274717 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