Natural Product: NPC471027

Natural Product IDNPC471027
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-P-(E)-Coumaroyl-5-(E)-Caffeoylquinic Acid
IUPAC Name (1R,3R,4S,5R)-3-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy-1,4-dihydroxy-5-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]oxycyclohexane-1-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2336739
PubChem CID 71717679
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000129] Alcohols and polyols
          • [CHEMONTID:0001292] Cyclic alcohols and derivatives
            • [CHEMONTID:0002509] Cyclitols and derivatives
              • [CHEMONTID:0002512] Quinic 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 LFZAQSKKPHEVOT-UMHPNHICSA-N
Standard InCHI InChI=1S/C25H24O11/c26-16-6-1-14(2-7-16)4-9-21(29)35-19-12-25(34,24(32)33)13-20(23(19)31)36-22(30)10-5-15-3-8-17(27)18(28)11-15/h1-11,19-20,23,26-28,31,34H,12-13H2,(H,32,33)/b9-4+,10-5+/t19-,20-,23+,25-/m1/s1
SMILES C1C(C(C(CC1(C(=O)O)O)OC(=O)C=CC2=CC(=C(C=C2)O)O)O)OC(=O)C=CC3=CC=C(C=C3)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   500.13 Volume:   482.978
?
Van der Waals volume.
Dense:   1.036 LogP:   1.723
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.642
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.281
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   23.0
TPSA:   191.05
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.183 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.037 Fsp3:   0.24
MCE-18:   77.903
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.702 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.049
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.662
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.549 Promiscuous compounds:   0.341

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.526 MDCK Permeability:   -5.067
Pgp-inhibitor:   0.0 Pgp-substrate:   0.042
PAMPA:   1.0
?
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):   0.612
20% Bioavailability (F20%):   0.999 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.866
Plasma Protein Binding (PPB):   70.293% Volume Distribution (VD):   0.813
Fu: 34.954%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.004
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.209
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.0
?
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):  2.349 Half-life (T1/2):  2.679

ADMET: Toxicity

hERG Blockers:  0.043 hERG Blockers (10um):  0.294
Human Hepatotoxicity (H-HT):  0.492 Drug-induced Liver Injury (DILI):  0.122
AMES Toxicity:  0.425 Rat Oral Acute Toxicity:  0.228
Maximum Recommended Daily Dose:  0.86 Skin Sensitization:  0.999
Carcinogencity:  0.041 Eye Corrosion:  0.0
Eye Irritation:  0.105 Respiratory Toxicity:  0.157
Drug-induced Neurotoxicity:  0.202 Ototoxicity:  0.905
Hematotoxicity:  0.006 Drug-induced Nephrotoxicity:  0.751
Genotoxicity:  0.263 RPMI-8226 Immunitoxicity:  0.036
A549 Cytotoxicity:  0.5 Hek293 Cytotoxicity:  0.697
BCF:   0.615
?
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:   3.369
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.591
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.277
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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
NPO32535 dracocephalum ruyschiana Species Lamiaceae Eukaryota aerial parts Mongolian n.a. PMID[23356964]

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
NPT1 Others Radical scavenging activity n.a. IC50 = 57400.0 nM PMID[23333151]

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 NPC471027 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
0.9245 High Similarity NPC13818
0.7667 Intermediate Similarity NPC477333
0.7377 Intermediate Similarity NPC37250
0.7377 Intermediate Similarity NPC142703
0.7377 Intermediate Similarity NPC152942
0.7377 Intermediate Similarity NPC9991
0.7377 Intermediate Similarity NPC302857
0.7377 Intermediate Similarity NPC600892
0.7077 Intermediate Similarity NPC477335
0.6721 Remote Similarity NPC219428
0.6462 Remote Similarity NPC206095
0.6462 Remote Similarity NPC35702
0.6462 Remote Similarity NPC224389
0.6377 Remote Similarity NPC220664
0.6034 Remote Similarity NPC224208
0.6034 Remote Similarity NPC41661
0.5968 Remote Similarity NPC258469
0.5968 Remote Similarity NPC43158
0.5968 Remote Similarity NPC610147
0.5882 Remote Similarity NPC278068
0.5882 Remote Similarity NPC477334
0.5833 Remote Similarity NPC297517
0.5797 Remote Similarity NPC284948
0.5797 Remote Similarity NPC303090
0.5797 Remote Similarity NPC301382
0.5797 Remote Similarity NPC37331
0.5753 Remote Similarity NPC42464
0.5672 Remote Similarity NPC319628
0.5652 Remote Similarity NPC283560
0.5652 Remote Similarity NPC24295
0.5645 Remote Similarity NPC488563
0.5616 Remote Similarity NPC156875
0.5606 Remote Similarity NPC68517
0.5588 Remote Similarity NPC279676
0.55 Remote Similarity NPC474275
0.5424 Remote Similarity NPC217052
0.5424 Remote Similarity NPC329344
0.5424 Remote Similarity NPC237506
0.5424 Remote Similarity NPC32626
0.5397 Remote Similarity NPC251407
0.5397 Remote Similarity NPC168653
0.5362 Remote Similarity NPC156709
0.525 Remote Similarity NPC145425
0.5246 Remote Similarity NPC147192
0.5231 Remote Similarity NPC470848
0.519 Remote Similarity NPC471076
0.5167 Remote Similarity NPC233669
0.5139 Remote Similarity NPC483141
0.5139 Remote Similarity NPC163883
0.5082 Remote Similarity NPC281277
0.5075 Remote Similarity NPC198388
0.5075 Remote Similarity NPC475695
0.5075 Remote Similarity NPC610418
0.5072 Remote Similarity NPC179505
0.5072 Remote Similarity NPC295492
0.5072 Remote Similarity NPC303683
0.5072 Remote Similarity NPC274891

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC471027 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
0.5797 Remote Similarity NPD6190 Approved

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