Natural Product: NPC474206

Natural Product IDNPC474206
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-5'-Hydroxy-7,3',4'-Trimethoxyflavan
IUPAC Name 2,3-dimethoxy-5-[(2S)-7-methoxy-3,4-dihydro-2H-chromen-2-yl]phenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL463469
PubChem CID 44567045
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 NOBIKWFGKRXGGQ-HNNXBMFYSA-N
Standard InCHI InChI=1S/C18H20O5/c1-20-13-6-4-11-5-7-15(23-16(11)10-13)12-8-14(19)18(22-3)17(9-12)21-2/h4,6,8-10,15,19H,5,7H2,1-3H3/t15-/m0/s1
SMILES COc1ccc2c(c1)O[C@@H](CC2)c1cc(O)c(c(c1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.13 Volume:   322.347
?
Van der Waals volume.
Dense:   0.981 LogP:   3.125
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.116
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.291
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   17.0
TPSA:   57.15
?
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:   0.936 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.767 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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.412 Fluc inhibitor:   0.928
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.047
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.21
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.306 Promiscuous compounds:   0.213

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.841 MDCK Permeability:   -4.725
Pgp-inhibitor:   0.608 Pgp-substrate:   0.034
PAMPA:   0.015
?
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):   0.004
20% Bioavailability (F20%):   0.127 30% Bioavailability (F30%):   0.103
50% Bioavailability (F50%):   0.885

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.305 MRP1:   0.95
Plasma Protein Binding (PPB):   96.532% Volume Distribution (VD):   -0.093
Fu: 3.17%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.938
OATP1B3 inhibitor:   0.984 BCRP inhibitor:   0.946
BSEP inhibitor:   0.961

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.983
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.798
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.929 CYP2D6-substrate:   0.822
CYP3A4-inhibitor:   0.989 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.064 CYP2C8-inhibitor:   1.0
HLM stability:   0.117
?
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):  5.599 Half-life (T1/2):  1.198

ADMET: Toxicity

hERG Blockers:  0.493 hERG Blockers (10um):  0.641
Human Hepatotoxicity (H-HT):  0.712 Drug-induced Liver Injury (DILI):  0.719
AMES Toxicity:  0.446 Rat Oral Acute Toxicity:  0.54
Maximum Recommended Daily Dose:  0.811 Skin Sensitization:  0.541
Carcinogencity:  0.529 Eye Corrosion:  0.005
Eye Irritation:  0.687 Respiratory Toxicity:  0.889
Drug-induced Neurotoxicity:  0.765 Ototoxicity:  0.532
Hematotoxicity:  0.377 Drug-induced Nephrotoxicity:  0.663
Genotoxicity:  0.259 RPMI-8226 Immunitoxicity:  0.173
A549 Cytotoxicity:  0.554 Hek293 Cytotoxicity:  0.511
BCF:   1.573
?
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:   3.762
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.723
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.533
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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
NPO8046 Muntingia calabura Species Muntingiaceae Eukaryota Roots n.a. n.a. PMID[2045815]
NPO8046 Muntingia calabura Species Muntingiaceae Eukaryota n.a. root n.a. PMID[2045815]
NPO8046 Muntingia calabura Species Muntingiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8046 Muntingia calabura Species Muntingiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8046 Muntingia calabura Species Muntingiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8046 Muntingia calabura Species Muntingiaceae 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
NPT168 Cell line P388 Mus musculus ED50 = 5.9 ug ml-1 PMID[26151487]
NPT91 Cell line KB Homo sapiens ED50 = 9.4 ug ml-1 PMID[15921441]
NPT91 Cell line KB Homo sapiens ED50 = 13.3 ug ml-1 PMID[8691203]
NPT147 Cell line SK-MEL-2 Homo sapiens ED50 = 14.6 ug ml-1 PMID[25008455]
NPT453 Cell line HT-1080 Homo sapiens ED50 > 20.0 ug ml-1 PMID[26123643]
NPT1034 Cell line Lu1 Homo sapiens ED50 > 20.0 ug ml-1 PMID[26123643]
NPT1851 Cell line Col2 Homo sapiens ED50 > 20.0 ug ml-1 PMID[26123643]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 > 20.0 ug ml-1 PMID[2045815]

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 NPC474206 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
0.7308 Intermediate Similarity NPC94750
0.6981 Remote Similarity NPC112939
0.6981 Remote Similarity NPC112246
0.6863 Remote Similarity NPC100099
0.5439 Remote Similarity NPC176051
0.5424 Remote Similarity NPC321657
0.5357 Remote Similarity NPC121812
0.5357 Remote Similarity NPC36016
0.5345 Remote Similarity NPC470356
0.5345 Remote Similarity NPC102904
0.5345 Remote Similarity NPC103976
0.5323 Remote Similarity NPC318373
0.5172 Remote Similarity NPC107551

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474206 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