Natural Product: NPC474875

Natural Product IDNPC474875
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HPJJCRNQEWRFQW-HTWICIHYSA-N
IUPAC Name n.a.
Synonyms Ethyl 4-O-Caffeoylquinate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL485994
PubChem CID n.a.
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 HPJJCRNQEWRFQW-HTWICIHYSA-N
Standard InCHI InChI=1S/C18H22O9/c1-2-26-17(24)18(25)8-13(21)16(14(22)9-18)27-15(23)6-4-10-3-5-11(19)12(20)7-10/h3-7,13-14,16,19-22,25H,2,8-9H2,1H3/b6-4+/t13-,14-,16-,18-/m1/s1
SMILES CCOC(=O)[C@]1(O)C[C@@H](O)[C@@H]([C@@H](C1)O)OC(=O)/C=C/c1ccc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   382.13 Volume:   366.065
?
Van der Waals volume.
Dense:   1.044 LogP:   1.425
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.759
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.161
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   15.0
TPSA:   153.75
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.265 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.59 Fsp3:   0.444
MCE-18:   58.846
?
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:   0.555 Fluc inhibitor:   0.916
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.219
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.339
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.335 Promiscuous compounds:   0.563

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.352 MDCK Permeability:   -5.181
Pgp-inhibitor:   0.001 Pgp-substrate:   0.027
PAMPA:   0.963
?
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):   0.032
20% Bioavailability (F20%):   0.991 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.47
Plasma Protein Binding (PPB):   69.676% Volume Distribution (VD):   -0.178
Fu: 29.623%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.01
BSEP inhibitor:   0.219

ADMET: Metabolism

CYP1A2-inhibitor:   0.013 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.18
CYP3A4-inhibitor:   0.021 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.039
HLM stability:   0.135
?
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):  9.135 Half-life (T1/2):  2.096

ADMET: Toxicity

hERG Blockers:  0.089 hERG Blockers (10um):  0.27
Human Hepatotoxicity (H-HT):  0.472 Drug-induced Liver Injury (DILI):  0.484
AMES Toxicity:  0.344 Rat Oral Acute Toxicity:  0.095
Maximum Recommended Daily Dose:  0.729 Skin Sensitization:  0.972
Carcinogencity:  0.421 Eye Corrosion:  0.004
Eye Irritation:  0.771 Respiratory Toxicity:  0.451
Drug-induced Neurotoxicity:  0.022 Ototoxicity:  0.786
Hematotoxicity:  0.029 Drug-induced Nephrotoxicity:  0.206
Genotoxicity:  0.428 RPMI-8226 Immunitoxicity:  0.024
A549 Cytotoxicity:  0.488 Hek293 Cytotoxicity:  0.172
BCF:   0.588
?
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:   3.234
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.868
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.249
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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
NPO32987 vittaria anguste-elongata Species Pteridaceae Eukaryota n.a. n.a. n.a. PMID[16124757]

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 = 234000.0 nM PMID[19114678]

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 NPC474875 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
0.8302 Intermediate Similarity NPC26241
0.7049 Intermediate Similarity NPC205751
0.6981 Remote Similarity NPC474275
0.6842 Remote Similarity NPC182217
0.6338 Remote Similarity NPC19380
0.6296 Remote Similarity NPC233669
0.619 Remote Similarity NPC277315
0.619 Remote Similarity NPC472016
0.619 Remote Similarity NPC192831
0.6182 Remote Similarity NPC281277
0.6176 Remote Similarity NPC146277
0.6071 Remote Similarity NPC309434
0.6071 Remote Similarity NPC224208
0.6071 Remote Similarity NPC41661
0.6034 Remote Similarity NPC605000
0.6 Remote Similarity NPC258469
0.6 Remote Similarity NPC43158
0.6 Remote Similarity NPC610147
0.5968 Remote Similarity NPC219428
0.5962 Remote Similarity NPC95381
0.5789 Remote Similarity NPC147192
0.5781 Remote Similarity NPC295492
0.5781 Remote Similarity NPC303683
0.5781 Remote Similarity NPC274891
0.5692 Remote Similarity NPC319628
0.5667 Remote Similarity NPC470849
0.5667 Remote Similarity NPC474895
0.5484 Remote Similarity NPC155209
0.5439 Remote Similarity NPC474967
0.5439 Remote Similarity NPC33749
0.5417 Remote Similarity NPC306343
0.5357 Remote Similarity NPC217472
0.5342 Remote Similarity NPC93498
0.5333 Remote Similarity NPC203124
0.5333 Remote Similarity NPC607366
0.5254 Remote Similarity NPC328593
0.5246 Remote Similarity NPC65791
0.5238 Remote Similarity NPC470848
0.5172 Remote Similarity NPC261453
0.5143 Remote Similarity NPC163883
0.5094 Remote Similarity NPC226250
0.5085 Remote Similarity NPC147654

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474875 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