Natural Product: NPC76465

Natural Product IDNPC76465
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7-Dimethoxy-40-Hydroxyflavan
IUPAC Name 4-[(2S)-5,7-dimethoxy-3,4-dihydro-2H-chromen-2-yl]phenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL397828
PubChem CID 14137569
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 AVMGPGZQJKDABF-HNNXBMFYSA-N
Standard InCHI InChI=1S/C17H18O4/c1-19-13-9-16(20-2)14-7-8-15(21-17(14)10-13)11-3-5-12(18)6-4-11/h3-6,9-10,15,18H,7-8H2,1-2H3/t15-/m0/s1
SMILES COc1cc2O[C@@H](CCc2c(c1)OC)c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.12 Volume:   296.261
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Van der Waals volume.
Dense:   0.966 LogP:   3.21
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.131
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.437
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   17.0
TPSA:   47.92
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.938 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.671 Fsp3:   0.294
MCE-18:   52.364
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.515 Fluc inhibitor:   0.727
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.107
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.267
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.315 Promiscuous compounds:   0.141

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.743 MDCK Permeability:   -4.728
Pgp-inhibitor:   0.508 Pgp-substrate:   0.572
PAMPA:   0.002
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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%):   0.012 30% Bioavailability (F30%):   0.071
50% Bioavailability (F50%):   0.547

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.908
Plasma Protein Binding (PPB):   88.788% Volume Distribution (VD):   0.028
Fu: 10.481%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.389
OATP1B3 inhibitor:   0.842 BCRP inhibitor:   0.993
BSEP inhibitor:   0.984

ADMET: Metabolism

CYP1A2-inhibitor:   0.693 CYP1A2-substrate:   0.882
CYP2C19-inhibitor:   0.993 CYP2C19-substrate:   0.597
CYP2C9-inhibitor:   0.845 CYP2C9-substrate:   0.16
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.937
CYP2B6-substrate:   0.05 CYP2C8-inhibitor:   0.605
HLM stability:   0.633
?
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):  10.705 Half-life (T1/2):  1.126

ADMET: Toxicity

hERG Blockers:  0.507 hERG Blockers (10um):  0.627
Human Hepatotoxicity (H-HT):  0.781 Drug-induced Liver Injury (DILI):  0.305
AMES Toxicity:  0.426 Rat Oral Acute Toxicity:  0.588
Maximum Recommended Daily Dose:  0.884 Skin Sensitization:  0.593
Carcinogencity:  0.414 Eye Corrosion:  0.014
Eye Irritation:  0.862 Respiratory Toxicity:  0.825
Drug-induced Neurotoxicity:  0.848 Ototoxicity:  0.404
Hematotoxicity:  0.136 Drug-induced Nephrotoxicity:  0.517
Genotoxicity:  0.604 RPMI-8226 Immunitoxicity:  0.107
A549 Cytotoxicity:  0.435 Hek293 Cytotoxicity:  0.571
BCF:   1.366
?
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:   3.923
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.002
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.402
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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
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota n.a. stem n.a. PMID[17077549]
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota stems n.a. n.a. PMID[17158054]
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]

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
NPT466 Cell line U-937 Homo sapiens IC50 = 39000.0 nM PMID[10425119]
NPT466 Cell line U-937 Homo sapiens IC50 = 40000.0 nM PMID[24087924]
NPT466 Cell line U-937 Homo sapiens IC50 = 10000.0 nM PMID[25221651]

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 NPC76465 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
0.7778 Intermediate Similarity NPC11060
0.7209 Intermediate Similarity NPC172253
0.7021 Intermediate Similarity NPC100099
0.6327 Remote Similarity NPC38761
0.62 Remote Similarity NPC188022
0.5957 Remote Similarity NPC59561
0.5957 Remote Similarity NPC93398
0.5957 Remote Similarity NPC258979
0.5957 Remote Similarity NPC8283
0.5686 Remote Similarity NPC36016
0.56 Remote Similarity NPC482472
0.5577 Remote Similarity NPC134195
0.5472 Remote Similarity NPC17809
0.5472 Remote Similarity NPC329203
0.5472 Remote Similarity NPC222342
0.5273 Remote Similarity NPC112246
0.5098 Remote Similarity NPC106914
0.5098 Remote Similarity NPC86502
0.5091 Remote Similarity NPC306441

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC76465 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