Natural Product: NPC470848

Natural Product IDNPC470848
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-(4'-Hydroxyphenyl)-Propyl Caffeate
IUPAC Name 4-(4-hydroxyphenyl)butan-2-yl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2269338
PubChem CID 11381853
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 SLQHWTMMMMIIMN-YRNVUSSQSA-N
Standard InCHI InChI=1S/C19H20O5/c1-13(2-3-14-4-8-16(20)9-5-14)24-19(23)11-7-15-6-10-17(21)18(22)12-15/h4-13,20-22H,2-3H2,1H3/b11-7+
SMILES CC(CCC1=CC=C(C=C1)O)OC(=O)C=CC2=CC(=C(C=C2)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.13 Volume:   342.927
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Van der Waals volume.
Dense:   0.957 LogP:   3.829
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.55
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.61
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   86.99
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.43 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.727 Fsp3:   0.211
MCE-18:   26.0
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.977 Fluc inhibitor:   1.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.119
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.694
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.685 Promiscuous compounds:   0.923

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.022 MDCK Permeability:   -4.752
Pgp-inhibitor:   0.068 Pgp-substrate:   0.028
PAMPA:   0.243
?
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):   0.007
20% Bioavailability (F20%):   0.907 30% Bioavailability (F30%):   0.98
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.631
Plasma Protein Binding (PPB):   86.545% Volume Distribution (VD):   -0.344
Fu: 12.255%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.18
BSEP inhibitor:   0.969

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.302
CYP2C19-inhibitor:   0.055 CYP2C19-substrate:   0.891
CYP2C9-inhibitor:   0.28 CYP2C9-substrate:   0.024
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.477 CYP3A4-substrate:   0.972
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.275
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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):  13.292 Half-life (T1/2):  1.324

ADMET: Toxicity

hERG Blockers:  0.411 hERG Blockers (10um):  0.864
Human Hepatotoxicity (H-HT):  0.544 Drug-induced Liver Injury (DILI):  0.1
AMES Toxicity:  0.54 Rat Oral Acute Toxicity:  0.129
Maximum Recommended Daily Dose:  0.717 Skin Sensitization:  0.999
Carcinogencity:  0.217 Eye Corrosion:  0.04
Eye Irritation:  0.92 Respiratory Toxicity:  0.113
Drug-induced Neurotoxicity:  0.236 Ototoxicity:  0.539
Hematotoxicity:  0.023 Drug-induced Nephrotoxicity:  0.25
Genotoxicity:  0.185 RPMI-8226 Immunitoxicity:  0.029
A549 Cytotoxicity:  0.788 Hek293 Cytotoxicity:  0.773
BCF:   1.24
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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:   4.275
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.097
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.907
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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 = 6.25 ug.mL-1 PMID[16933864]
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[18500841]
NPT4635 Organism Colletotrichum truncatum Colletotrichum truncatum MIC > 50.0 ug.mL-1 PMID[17404003]

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 NPC470848 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 NPC470849
0.68 Remote Similarity NPC233669
0.6667 Remote Similarity NPC281277
0.6538 Remote Similarity NPC309434
0.614 Remote Similarity NPC155209
0.5926 Remote Similarity NPC474275
0.5926 Remote Similarity NPC86198
0.5893 Remote Similarity NPC168799
0.5714 Remote Similarity NPC277394
0.5636 Remote Similarity NPC147192
0.5636 Remote Similarity NPC224208
0.5636 Remote Similarity NPC41661
0.5574 Remote Similarity NPC610
0.5574 Remote Similarity NPC175799
0.551 Remote Similarity NPC226250
0.549 Remote Similarity NPC95381
0.5455 Remote Similarity NPC147654
0.5397 Remote Similarity NPC600402
0.5312 Remote Similarity NPC611548
0.5303 Remote Similarity NPC601257
0.5273 Remote Similarity NPC474967
0.5273 Remote Similarity NPC33749
0.5246 Remote Similarity NPC26241
0.5238 Remote Similarity NPC474875
0.5231 Remote Similarity NPC471027
0.5231 Remote Similarity NPC279676
0.5231 Remote Similarity NPC477333
0.5205 Remote Similarity NPC28776
0.5185 Remote Similarity NPC70084
0.5167 Remote Similarity NPC200988
0.5167 Remote Similarity NPC145023
0.5147 Remote Similarity NPC610018
0.5088 Remote Similarity NPC328593
0.5085 Remote Similarity NPC65791
0.5082 Remote Similarity NPC258469
0.5082 Remote Similarity NPC43158
0.5082 Remote Similarity NPC610147
0.5079 Remote Similarity NPC219428
0.5075 Remote Similarity NPC477334
0.5072 Remote Similarity NPC603702

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470848 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