Natural Product: NPC163898

Natural Product IDNPC163898
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Glycosmisic Acid
IUPAC Name (E)-3-[(2S,3R)-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]prop-2-enoic acid
Synonyms Glycosmisic Acid
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2346742
PubChem CID 38356809
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 FHYQIQMSODIFCP-ZMOFONSMSA-N
Standard InCHI InChI=1S/C20H20O7/c1-25-16-9-12(4-5-15(16)22)19-14(10-21)13-7-11(3-6-18(23)24)8-17(26-2)20(13)27-19/h3-9,14,19,21-22H,10H2,1-2H3,(H,23,24)/b6-3+/t14-,19+/m0/s1
SMILES OC[C@@H]1[C@H](Oc2c1cc(/C=C/C(=O)O)cc2OC)c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.12 Volume:   369.247
?
Van der Waals volume.
Dense:   1.008 LogP:   2.449
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.327
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.471
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   105.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.67 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.324 Fsp3:   0.25
MCE-18:   60.04
?
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:   0.789 Fluc inhibitor:   0.997
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.166
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.597
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.284 Promiscuous compounds:   0.398

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.104 MDCK Permeability:   -4.842
Pgp-inhibitor:   0.022 Pgp-substrate:   0.044
PAMPA:   0.407
?
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):   0.038
20% Bioavailability (F20%):   0.711 30% Bioavailability (F30%):   0.901
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.417
Plasma Protein Binding (PPB):   67.645% Volume Distribution (VD):   -0.478
Fu: 29.369%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.494
BSEP inhibitor:   0.869

ADMET: Metabolism

CYP1A2-inhibitor:   0.856 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.71 CYP2C19-substrate:   0.112
CYP2C9-inhibitor:   0.746 CYP2C9-substrate:   0.013
CYP2D6-inhibitor:   0.648 CYP2D6-substrate:   0.221
CYP3A4-inhibitor:   0.025 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.776
HLM stability:   0.117
?
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):  5.039 Half-life (T1/2):  2.256

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.038
Human Hepatotoxicity (H-HT):  0.862 Drug-induced Liver Injury (DILI):  0.721
AMES Toxicity:  0.373 Rat Oral Acute Toxicity:  0.136
Maximum Recommended Daily Dose:  0.368 Skin Sensitization:  0.851
Carcinogencity:  0.297 Eye Corrosion:  0.003
Eye Irritation:  0.954 Respiratory Toxicity:  0.347
Drug-induced Neurotoxicity:  0.181 Ototoxicity:  0.738
Hematotoxicity:  0.458 Drug-induced Nephrotoxicity:  0.687
Genotoxicity:  0.436 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.06 Hek293 Cytotoxicity:  0.12
BCF:   0.292
?
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:   2.931
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.395
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.588
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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
NPO28043 Streblus asper Species Moraceae Eukaryota Roots n.a. n.a. PMID[23434030]
NPO30830 Sphingobium sp. Species Sphingomonadaceae Bacteria n.a. n.a. n.a. PMID[26362985]
NPO28043 Streblus asper Species Moraceae Eukaryota n.a. n.a. n.a. PMID[4093781]
NPO28043 Streblus asper Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28043 Streblus asper Species Moraceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT963 Organism Hepatitis B virus Hepatitis B virus IC50 > 1000000.0 nM PMID[23434030]

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 NPC163898 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
0.746 Intermediate Similarity NPC284881
0.746 Intermediate Similarity NPC93433
0.746 Intermediate Similarity NPC474444
0.7419 Intermediate Similarity NPC156502
0.7419 Intermediate Similarity NPC10737
0.7231 Intermediate Similarity NPC206413
0.7231 Intermediate Similarity NPC482649
0.7231 Intermediate Similarity NPC149003
0.7231 Intermediate Similarity NPC482647
0.7231 Intermediate Similarity NPC482648
0.7231 Intermediate Similarity NPC482651
0.7231 Intermediate Similarity NPC194244
0.7231 Intermediate Similarity NPC482650
0.697 Remote Similarity NPC253878
0.697 Remote Similarity NPC471414
0.6406 Remote Similarity NPC300757
0.6364 Remote Similarity NPC177160
0.6154 Remote Similarity NPC87725
0.6154 Remote Similarity NPC263261
0.6119 Remote Similarity NPC473408
0.6119 Remote Similarity NPC29799
0.6119 Remote Similarity NPC263367
0.6119 Remote Similarity NPC54743
0.6056 Remote Similarity NPC126206
0.6029 Remote Similarity NPC472961
0.6029 Remote Similarity NPC472962
0.6 Remote Similarity NPC187616
0.6 Remote Similarity NPC193026
0.6 Remote Similarity NPC49603
0.5634 Remote Similarity NPC209985
0.5588 Remote Similarity NPC26394
0.5556 Remote Similarity NPC470769
0.5541 Remote Similarity NPC480707
0.55 Remote Similarity NPC70744
0.55 Remote Similarity NPC260397
0.5422 Remote Similarity NPC470828
0.5333 Remote Similarity NPC131971
0.5333 Remote Similarity NPC15189
0.5303 Remote Similarity NPC481090
0.5172 Remote Similarity NPC470827
0.5125 Remote Similarity NPC469889
0.5106 Remote Similarity NPC228357
0.5062 Remote Similarity NPC236166

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC163898 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