Natural Product: NPC470849

Natural Product IDNPC470849
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1-Methyl-3-(3',4'-Dihydroxyphenyl)-Propyl Caffeate
IUPAC Name 4-(3,4-dihydroxyphenyl)butan-2-yl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2269339
PubChem CID 11450770
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 JUZFAKSVZZEOIL-RMKNXTFCSA-N
Standard InCHI InChI=1S/C19H20O6/c1-12(2-3-13-4-7-15(20)17(22)10-13)25-19(24)9-6-14-5-8-16(21)18(23)11-14/h4-12,20-23H,2-3H2,1H3/b9-6+
SMILES CC(OC(=O)/C=C/c1ccc(c(c1)O)O)CCc1ccc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.13 Volume:   351.717
?
Van der Waals volume.
Dense:   0.978 LogP:   3.416
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.417
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.368
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   107.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.364 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.879 Fsp3:   0.211
MCE-18:   28.0
?
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:   0.973 Fluc inhibitor:   0.998
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.135
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.569
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.658 Promiscuous compounds:   0.92

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.344 MDCK Permeability:   -4.842
Pgp-inhibitor:   0.084 Pgp-substrate:   0.001
PAMPA:   0.064
?
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):   0.119
20% Bioavailability (F20%):   0.999 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.116
Plasma Protein Binding (PPB):   80.728% Volume Distribution (VD):   -0.179
Fu: 15.665%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.364
BSEP inhibitor:   0.909

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.024
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.148
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.719
?
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):  16.703 Half-life (T1/2):  1.49

ADMET: Toxicity

hERG Blockers:  0.284 hERG Blockers (10um):  0.881
Human Hepatotoxicity (H-HT):  0.504 Drug-induced Liver Injury (DILI):  0.463
AMES Toxicity:  0.585 Rat Oral Acute Toxicity:  0.114
Maximum Recommended Daily Dose:  0.797 Skin Sensitization:  1.0
Carcinogencity:  0.264 Eye Corrosion:  0.067
Eye Irritation:  0.959 Respiratory Toxicity:  0.085
Drug-induced Neurotoxicity:  0.028 Ototoxicity:  0.782
Hematotoxicity:  0.023 Drug-induced Nephrotoxicity:  0.072
Genotoxicity:  0.667 RPMI-8226 Immunitoxicity:  0.01
A549 Cytotoxicity:  0.935 Hek293 Cytotoxicity:  0.526
BCF:   1.292
?
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:   4.435
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.51
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.324
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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
NPO32673 zuccagnia punctata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[15161186]

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
NPT962 Organism Alternaria alternata Alternaria alternata MIC > 50.0 ug.mL-1 PMID[24742203]
NPT4636 Organism Diaporthe longicolla Diaporthe longicolla MIC > 50.0 ug.mL-1 PMID[24742203]
NPT4304 Organism Macrophomina phaseolina Macrophomina phaseolina MIC > 50.0 ug.mL-1 PMID[17404003]
NPT3685 Organism Fusarium equiseti Fusarium equiseti MIC > 50.0 ug.mL-1 PMID[24900628]
NPT1276 Organism Gibberella zeae Gibberella zeae MIC > 50.0 ug.mL-1 PMID[10560729]
NPT4635 Organism Colletotrichum truncatum Colletotrichum truncatum MIC > 50.0 ug.mL-1 PMID[16252909]

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 NPC470849 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
0.875 High Similarity NPC470848
0.7083 Intermediate Similarity NPC233669
0.6939 Remote Similarity NPC281277
0.68 Remote Similarity NPC309434
0.6667 Remote Similarity NPC155209
0.6415 Remote Similarity NPC168799
0.6154 Remote Similarity NPC474275
0.6 Remote Similarity NPC70084
0.5962 Remote Similarity NPC147654
0.5849 Remote Similarity NPC147192
0.5849 Remote Similarity NPC224208
0.5849 Remote Similarity NPC41661
0.5833 Remote Similarity NPC600402
0.5781 Remote Similarity NPC610018
0.5745 Remote Similarity NPC226250
0.5738 Remote Similarity NPC611548
0.5714 Remote Similarity NPC95381
0.5692 Remote Similarity NPC603702
0.569 Remote Similarity NPC26241
0.5667 Remote Similarity NPC474875
0.5556 Remote Similarity NPC299252
0.5556 Remote Similarity NPC86198
0.5517 Remote Similarity NPC258469
0.5517 Remote Similarity NPC43158
0.5517 Remote Similarity NPC610147
0.55 Remote Similarity NPC610
0.55 Remote Similarity NPC175799
0.5472 Remote Similarity NPC474967
0.5472 Remote Similarity NPC33749
0.5397 Remote Similarity NPC600415
0.5294 Remote Similarity NPC607186
0.5273 Remote Similarity NPC328593
0.5263 Remote Similarity NPC65791
0.5254 Remote Similarity NPC18074
0.5254 Remote Similarity NPC5419
0.5254 Remote Similarity NPC25581
0.5254 Remote Similarity NPC61
0.5246 Remote Similarity NPC288452
0.5246 Remote Similarity NPC219428
0.5231 Remote Similarity NPC600476
0.5231 Remote Similarity NPC607212
0.5217 Remote Similarity NPC605023
0.5185 Remote Similarity NPC261453
0.5179 Remote Similarity NPC263386
0.5179 Remote Similarity NPC141791
0.5172 Remote Similarity NPC488563
0.5172 Remote Similarity NPC474895
0.5156 Remote Similarity NPC486819
0.5139 Remote Similarity NPC28776
0.5094 Remote Similarity NPC217472
0.5094 Remote Similarity NPC150610
0.5088 Remote Similarity NPC203124
0.5088 Remote Similarity NPC607366
0.5079 Remote Similarity NPC179505
0.5079 Remote Similarity NPC295492
0.5079 Remote Similarity NPC303683
0.5079 Remote Similarity NPC274891
0.5077 Remote Similarity NPC205751

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470849 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