Natural Product: NPC470572

Natural Product IDNPC470572
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6'-Ocaffeoylgoodyeroside
IUPAC Name [(2R,3S,4S,5R,6R)-3,4,5-trihydroxy-6-[(3S)-5-oxooxolan-3-yl]oxyoxan-2-yl]methyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms 6'-Ocaffeoylgoodyeroside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2071306
PubChem CID 70693126
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 CYEFUTNNSBRMEB-ICCSCHITSA-N
Standard InCHI InChI=1S/C19H22O11/c20-11-3-1-9(5-12(11)21)2-4-14(22)28-8-13-16(24)17(25)18(26)19(30-13)29-10-6-15(23)27-7-10/h1-5,10,13,16-21,24-26H,6-8H2/b4-2+/t10-,13+,16+,17-,18+,19+/m0/s1
SMILES O=C1OC[C@H](C1)O[C@@H]1O[C@H](COC(=O)/C=C/c2ccc(c(c2)O)O)[C@H]([C@@H]([C@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   426.12 Volume:   392.385
?
Van der Waals volume.
Dense:   1.086 LogP:   -0.022
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.728
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.152
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   172.21
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.21 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.167 Fsp3:   0.474
MCE-18:   71.429
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.764 Fluc inhibitor:   0.657
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.2
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.354
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.259 Promiscuous compounds:   0.422

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.35 MDCK Permeability:   -5.258
Pgp-inhibitor:   0.004 Pgp-substrate:   0.282
PAMPA:   0.983
?
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):   0.131
20% Bioavailability (F20%):   0.955 30% Bioavailability (F30%):   0.989
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.078
Plasma Protein Binding (PPB):   64.533% Volume Distribution (VD):   -0.332
Fu: 35.567%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.987
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.037
BSEP inhibitor:   0.055

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.338
?
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):  2.244 Half-life (T1/2):  2.645

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.394
Human Hepatotoxicity (H-HT):  0.678 Drug-induced Liver Injury (DILI):  0.981
AMES Toxicity:  0.95 Rat Oral Acute Toxicity:  0.076
Maximum Recommended Daily Dose:  0.516 Skin Sensitization:  1.0
Carcinogencity:  0.646 Eye Corrosion:  0.037
Eye Irritation:  0.894 Respiratory Toxicity:  0.025
Drug-induced Neurotoxicity:  0.191 Ototoxicity:  0.75
Hematotoxicity:  0.064 Drug-induced Nephrotoxicity:  0.97
Genotoxicity:  0.948 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.806 Hek293 Cytotoxicity:  0.294
BCF:   0.607
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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:   3.284
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.91
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.424
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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
NPO33136 sarracenia purpurea Species Sarraceniaceae Eukaryota n.a. n.a. n.a. PMID[22738356]

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
NPT6482 Individual protein Glucose-6-phosphatase Rattus norvegicus IC50 = 13900.0 nM PMID[26241103]
NPT6482 Individual protein Glucose-6-phosphatase Rattus norvegicus Inhibition = 44.0 % PMID[8158166]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC470572 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
0.7273 Intermediate Similarity NPC229784
0.7164 Intermediate Similarity NPC287597
0.6866 Remote Similarity NPC479473
0.6866 Remote Similarity NPC275721
0.6866 Remote Similarity NPC479468
0.6866 Remote Similarity NPC479474
0.6761 Remote Similarity NPC219677
0.6714 Remote Similarity NPC34293
0.6533 Remote Similarity NPC220942
0.64 Remote Similarity NPC476867
0.6377 Remote Similarity NPC288416
0.625 Remote Similarity NPC157898
0.6197 Remote Similarity NPC473924
0.6154 Remote Similarity NPC476873
0.6104 Remote Similarity NPC476864
0.6081 Remote Similarity NPC252114
0.6056 Remote Similarity NPC477293
0.5949 Remote Similarity NPC64141
0.5949 Remote Similarity NPC205195
0.5949 Remote Similarity NPC476868
0.5938 Remote Similarity NPC232880
0.5882 Remote Similarity NPC69367
0.5844 Remote Similarity NPC291296
0.5714 Remote Similarity NPC184633
0.5696 Remote Similarity NPC157816
0.5679 Remote Similarity NPC476870
0.5641 Remote Similarity NPC281798
0.5625 Remote Similarity NPC476866
0.5616 Remote Similarity NPC477294
0.5542 Remote Similarity NPC265648
0.5541 Remote Similarity NPC78363
0.5467 Remote Similarity NPC474641
0.5467 Remote Similarity NPC291153
0.5333 Remote Similarity NPC217472
0.5316 Remote Similarity NPC225307
0.5309 Remote Similarity NPC235294
0.5294 Remote Similarity NPC488081
0.5294 Remote Similarity NPC476872
0.5287 Remote Similarity NPC476871
0.5244 Remote Similarity NPC226005
0.5244 Remote Similarity NPC476869
0.5238 Remote Similarity NPC224208
0.5238 Remote Similarity NPC41661
0.5238 Remote Similarity NPC476865
0.5233 Remote Similarity NPC300262
0.5231 Remote Similarity NPC65791
0.5211 Remote Similarity NPC52097
0.5185 Remote Similarity NPC28637
0.5176 Remote Similarity NPC83743
0.5172 Remote Similarity NPC133984
0.5169 Remote Similarity NPC611523
0.5165 Remote Similarity NPC171706
0.5152 Remote Similarity NPC474895
0.5122 Remote Similarity NPC204937
0.5116 Remote Similarity NPC476383
0.5114 Remote Similarity NPC125823
0.5114 Remote Similarity NPC7145
0.5114 Remote Similarity NPC143480
0.5085 Remote Similarity NPC95381
0.5075 Remote Similarity NPC11724
0.507 Remote Similarity NPC470825
0.5062 Remote Similarity NPC10205

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470572 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