Natural Product: NPC322752

Natural Product IDNPC322752
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Protocatechuic acid 4-glucoside
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic glycosides

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 HFFREILXLCWCQH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C13H16O9/c14-4-8-9(16)10(17)11(18)13(22-8)21-7-2-1-5(12(19)20)3-6(7)15/h1-3,8-11,13-18H,4H2,(H,19,20)
SMILES OCC1OC(OC2=C(O)C=C(C=C2)C(O)=O)C(O)C(O)C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.08 Volume:   284.858
?
Van der Waals volume.
Dense:   1.11 LogP:   -1.567
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.348
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.21
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   156.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   6.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.38 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.475 Fsp3:   0.462
MCE-18:   52.895
?
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:   0
Colloidal aggregators:   0.004 Fluc inhibitor:   0.034
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.123
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.328
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.391 Promiscuous compounds:   0.873

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.329 MDCK Permeability:   -5.044
Pgp-inhibitor:   0.0 Pgp-substrate:   0.572
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):   0.985
20% Bioavailability (F20%):   0.678 30% Bioavailability (F30%):   0.953
50% Bioavailability (F50%):   0.938

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.982
Plasma Protein Binding (PPB):   36.786% Volume Distribution (VD):   -0.622
Fu: 69.702%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.004
OATP1B3 inhibitor:   0.737 BCRP inhibitor:   0.005
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.871 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.045
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):  2.248 Half-life (T1/2):  2.772

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.067
Human Hepatotoxicity (H-HT):  0.519 Drug-induced Liver Injury (DILI):  0.603
AMES Toxicity:  0.433 Rat Oral Acute Toxicity:  0.205
Maximum Recommended Daily Dose:  0.052 Skin Sensitization:  0.19
Carcinogencity:  0.165 Eye Corrosion:  0.0
Eye Irritation:  0.646 Respiratory Toxicity:  0.107
Drug-induced Neurotoxicity:  0.13 Ototoxicity:  0.932
Hematotoxicity:  0.143 Drug-induced Nephrotoxicity:  0.275
Genotoxicity:  0.091 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.015 Hek293 Cytotoxicity:  0.053
BCF:   0.133
?
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:   2.11
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.59
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.96
?
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
NPO3347 Vaccinium corymbosum Species Ericaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.ecoenv.2016.07.029]
NPO1751 Ribes nigrum Species n.a. n.a. Fruit n.a. n.a. DOI[10.1016/S0963-9969(99)00095-2]
NPO3347 Vaccinium corymbosum Species Ericaceae Eukaryota Fruit n.a. n.a. DOI[10.1016/S0963-9969(99)00095-2]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. fruit n.a. PMID[16417304]
NPO3347 Vaccinium corymbosum Species Ericaceae Eukaryota n.a. fruit n.a. PMID[21648406]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. n.a. PMID[36557810]
NPO3347 Vaccinium corymbosum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27436 Ribes uva-crispa Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO1751 Ribes nigrum Species n.a. n.a. Fruit Juice n.a. n.a. Database[FooDB]
NPO27436 Ribes uva-crispa Species n.a. n.a. Fruits n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Fruits n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota Fruits n.a. Database[FooDB]
NPO42025 Ribes nidigrolaria Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO3347 Vaccinium corymbosum Species Ericaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Seed Essent. Oil n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Seed n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Leaf n.a. n.a. Database[FooDB]
NPO3347 Vaccinium corymbosum Species Ericaceae Eukaryota Fruit Juice n.a. n.a. Database[FooDB]
NPO3347 Vaccinium corymbosum Species Ericaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO27436 Ribes uva-crispa Species n.a. n.a. Fruit n.a. n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Fruit n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Bulb n.a. n.a. Database[FooDB]
NPO27436 Ribes uva-crispa Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO3347 Vaccinium corymbosum Species Ericaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO3347 Vaccinium corymbosum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27436 Ribes uva-crispa Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]

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
NPO16038 Ribes rubrum Raw n.a. 0.066666668 n.a. n.a. mg/100g Database [PHENOL EXPLORER]
NPO1751 Ribes nigrum Raw n.a. 0.066666668 n.a. n.a. mg/100g Database [PHENOL EXPLORER]
NPO27436 Ribes uva-crispa Raw n.a. 0.449999996 n.a. n.a. mg/100g Database [PHENOL EXPLORER]
NPO3347 Vaccinium corymbosum Raw n.a. 0.400000006 n.a. n.a. mg/100g Database [PHENOL EXPLORER]
NPO42025 Ribes nidigrolaria Raw n.a. 0.400000006 n.a. n.a. mg/100g Database [PHENOL EXPLORER]

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

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 NPC322752 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
0.6379 Remote Similarity NPC83975
0.6296 Remote Similarity NPC9248
0.5938 Remote Similarity NPC186418
0.5574 Remote Similarity NPC19470
0.5484 Remote Similarity NPC481303
0.5455 Remote Similarity NPC142319
0.5424 Remote Similarity NPC221090
0.5385 Remote Similarity NPC100389
0.5357 Remote Similarity NPC484157
0.5323 Remote Similarity NPC205054
0.5312 Remote Similarity NPC25292
0.5283 Remote Similarity NPC228907
0.527 Remote Similarity NPC76112
0.527 Remote Similarity NPC170018
0.527 Remote Similarity NPC92403
0.527 Remote Similarity NPC66820
0.5263 Remote Similarity NPC192810
0.5231 Remote Similarity NPC59324
0.5224 Remote Similarity NPC202700
0.5211 Remote Similarity NPC185103
0.5079 Remote Similarity NPC251102
0.5079 Remote Similarity NPC210298

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC322752 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
0.527 Remote Similarity NPD8312 Approved
0.527 Remote Similarity NPD8313 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