Natural Product: NPC106406

Natural Product IDNPC106406
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-(3,4-Dihydroxyphenyl)Acrylic Acid 1-(3,4-Dihydroxyphenyl)-2-Methoxycarbonylethyl Ester
IUPAC Name methyl (3S)-3-(3,4-dihydroxyphenyl)-3-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxypropanoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL478941
PubChem CID 10452024
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0000059] Coumaric acids and derivatives

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 OSDXSOSJRPQCHJ-GALSZHCDSA-N
Standard InCHI InChI=1S/C19H18O8/c1-26-19(25)10-17(12-4-6-14(21)16(23)9-12)27-18(24)7-3-11-2-5-13(20)15(22)8-11/h2-9,17,20-23H,10H2,1H3/b7-3+/t17-/m0/s1
SMILES COC(=O)C[C@@H](c1ccc(c(c1)O)O)OC(=O)/C=C/c1ccc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.1 Volume:   366.661
?
Van der Waals volume.
Dense:   1.02 LogP:   2.391
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.551
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.032
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   15.0
TPSA:   133.52
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.344 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.011 Fsp3:   0.158
MCE-18:   30.0
?
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:   1
Colloidal aggregators:   0.943 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.166
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.56
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.565 Promiscuous compounds:   0.381

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.555 MDCK Permeability:   -4.917
Pgp-inhibitor:   0.002 Pgp-substrate:   0.0
PAMPA:   0.972
?
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):   0.016
20% Bioavailability (F20%):   0.875 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.199
Plasma Protein Binding (PPB):   84.493% Volume Distribution (VD):   -0.309
Fu: 13.589%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.731
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.014
BSEP inhibitor:   0.667

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.039
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.008
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.991
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.854
?
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):  18.703 Half-life (T1/2):  1.919

ADMET: Toxicity

hERG Blockers:  0.137 hERG Blockers (10um):  0.702
Human Hepatotoxicity (H-HT):  0.686 Drug-induced Liver Injury (DILI):  0.615
AMES Toxicity:  0.527 Rat Oral Acute Toxicity:  0.343
Maximum Recommended Daily Dose:  0.873 Skin Sensitization:  0.999
Carcinogencity:  0.08 Eye Corrosion:  0.048
Eye Irritation:  0.96 Respiratory Toxicity:  0.196
Drug-induced Neurotoxicity:  0.252 Ototoxicity:  0.601
Hematotoxicity:  0.034 Drug-induced Nephrotoxicity:  0.382
Genotoxicity:  0.985 RPMI-8226 Immunitoxicity:  0.011
A549 Cytotoxicity:  0.826 Hek293 Cytotoxicity:  0.173
BCF:   0.863
?
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:   3.851
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.089
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.777
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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
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. whole plant n.a. PMID[10896056]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[11374970]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[17338565]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[21273070]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[22066578]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26913 Isodon excisus 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
NPT466 Cell line U-937 Homo sapiens IC50 = 52.4 ug.mL-1 PMID[19223615]

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 NPC106406 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
0.6591 Remote Similarity NPC226250
0.5577 Remote Similarity NPC233669
0.5577 Remote Similarity NPC33749
0.5556 Remote Similarity NPC318799
0.551 Remote Similarity NPC95381
0.5345 Remote Similarity NPC258469
0.5345 Remote Similarity NPC43158
0.5345 Remote Similarity NPC610147
0.5319 Remote Similarity NPC253746
0.5283 Remote Similarity NPC261453
0.5283 Remote Similarity NPC474967
0.5254 Remote Similarity NPC26241
0.5192 Remote Similarity NPC217472
0.5192 Remote Similarity NPC150610
0.5185 Remote Similarity NPC281277
0.5091 Remote Similarity NPC328593
0.5091 Remote Similarity NPC474275
0.5091 Remote Similarity NPC309434
0.5091 Remote Similarity NPC224208
0.5091 Remote Similarity NPC41661
0.5088 Remote Similarity NPC168799
0.5068 Remote Similarity NPC471076
0.5068 Remote Similarity NPC192568

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC106406 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