Natural Product: NPC191046

Natural Product IDNPC191046
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Vanilloyl Calleryanin
IUPAC Name [3-hydroxy-4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]methyl 4-hydroxy-3-methoxybenzoate
Synonyms Vanilloylcalleryanin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL515507
PubChem CID 5315170
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000238] Tannins
        • [CHEMONTID:0001710] Hydrolyzable tannins

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 AWNIZJLTUVSVCI-GQUPQBGVSA-N
Standard InCHI InChI=1S/C21H24O11/c1-29-15-7-11(3-4-12(15)23)20(28)30-9-10-2-5-14(13(24)6-10)31-21-19(27)18(26)17(25)16(8-22)32-21/h2-7,16-19,21-27H,8-9H2,1H3/t16-,17-,18+,19-,21-/m1/s1
SMILES OC[C@H]1O[C@@H](Oc2ccc(cc2O)COC(=O)c2ccc(c(c2)OC)O)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   452.13 Volume:   424.34
?
Van der Waals volume.
Dense:   1.065 LogP:   1.034
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.445
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.66
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   19.0
TPSA:   175.37
?
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:   0.303 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.609 Fsp3:   0.381
MCE-18:   70.241
?
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:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.444 Fluc inhibitor:   0.283
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.135
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.472
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.141 Promiscuous compounds:   0.355

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.141 MDCK Permeability:   -5.287
Pgp-inhibitor:   0.001 Pgp-substrate:   0.004
PAMPA:   0.925
?
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):   0.279
20% Bioavailability (F20%):   0.555 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   0.938

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.013 MRP1:   0.452
Plasma Protein Binding (PPB):   80.772% Volume Distribution (VD):   -0.273
Fu: 18.581%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.013
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.015 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.007
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.121
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.952
HLM stability:   0.062
?
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):  3.572 Half-life (T1/2):  2.974

ADMET: Toxicity

hERG Blockers:  0.035 hERG Blockers (10um):  0.199
Human Hepatotoxicity (H-HT):  0.136 Drug-induced Liver Injury (DILI):  0.799
AMES Toxicity:  0.73 Rat Oral Acute Toxicity:  0.006
Maximum Recommended Daily Dose:  0.024 Skin Sensitization:  0.988
Carcinogencity:  0.364 Eye Corrosion:  0.0
Eye Irritation:  0.35 Respiratory Toxicity:  0.01
Drug-induced Neurotoxicity:  0.007 Ototoxicity:  0.816
Hematotoxicity:  0.037 Drug-induced Nephrotoxicity:  0.372
Genotoxicity:  0.066 RPMI-8226 Immunitoxicity:  0.15
A549 Cytotoxicity:  0.175 Hek293 Cytotoxicity:  0.323
BCF:   0.514
?
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:   3.278
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.497
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.926
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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
NPO33279 ilex litseaefolia Species Aquifoliaceae Eukaryota stems n.a. n.a. PMID[16252920]
NPO8101 Rehmannia glutinosa Species Orobanchaceae Eukaryota Roots n.a. n.a. PMID[22916954]
NPO8101 Rehmannia glutinosa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8101 Rehmannia glutinosa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28586 Pyrus calleryana Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8101 Rehmannia glutinosa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28586 Pyrus calleryana Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8101 Rehmannia glutinosa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28586 Pyrus calleryana Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8101 Rehmannia glutinosa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8101 Rehmannia glutinosa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28586 Pyrus calleryana Species Rosaceae Eukaryota 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

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
NPT60 Individual protein Lysosomal alpha-glucosidase Homo sapiens IC50 > 100.0 ug.mL-1 PMID[16252920]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. IC50 > 100.0 ug.mL-1 PMID[16252920]

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 NPC191046 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
0.75 Intermediate Similarity NPC194095
0.6585 Remote Similarity NPC133984
0.5974 Remote Similarity NPC232228
0.5797 Remote Similarity NPC105827
0.5735 Remote Similarity NPC205054
0.5733 Remote Similarity NPC92054
0.5652 Remote Similarity NPC210015
0.5652 Remote Similarity NPC481303
0.5556 Remote Similarity NPC100389
0.5513 Remote Similarity NPC217950
0.5507 Remote Similarity NPC19470
0.5467 Remote Similarity NPC212770
0.5467 Remote Similarity NPC302989
0.5455 Remote Similarity NPC299435
0.5441 Remote Similarity NPC310661
0.5385 Remote Similarity NPC9248
0.5373 Remote Similarity NPC221090
0.5316 Remote Similarity NPC260604
0.5301 Remote Similarity NPC199928
0.527 Remote Similarity NPC469661
0.527 Remote Similarity NPC65530
0.5263 Remote Similarity NPC98777
0.5205 Remote Similarity NPC59324
0.52 Remote Similarity NPC202700
0.5128 Remote Similarity NPC116229
0.5125 Remote Similarity NPC311803
0.5075 Remote Similarity NPC609376
0.5065 Remote Similarity NPC189115
0.5065 Remote Similarity NPC106944
0.5063 Remote Similarity NPC186406
0.5062 Remote Similarity NPC38041
0.5062 Remote Similarity NPC18979
0.5062 Remote Similarity NPC22150
0.5062 Remote Similarity NPC147596
0.506 Remote Similarity NPC298847

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC191046 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