Natural Product: NPC65833

Natural Product IDNPC65833
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Flacourtoside A
IUPAC Name [(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(4-hydroxyphenoxy)oxan-2-yl]methyl benzoate
Synonyms Flacourtoside A
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2036483
PubChem CID 21672233
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 ZNWJKOJJZQDPSW-OGJJZOIMSA-N
Standard InCHI InChI=1S/C19H20O8/c20-12-6-8-13(9-7-12)26-19-17(23)16(22)15(21)14(27-19)10-25-18(24)11-4-2-1-3-5-11/h1-9,14-17,19-23H,10H2/t14-,15-,16+,17-,19-/m1/s1
SMILES c1ccc(cc1)C(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@H](Oc2ccc(cc2)O)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   376.12 Volume:   363.377
?
Van der Waals volume.
Dense:   1.035 LogP:   0.755
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.08
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.188
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   125.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.554 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.291 Fsp3:   0.316
MCE-18:   61.2
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.436 Fluc inhibitor:   0.532
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.149
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.07
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.297 Promiscuous compounds:   0.296

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.12 MDCK Permeability:   -4.875
Pgp-inhibitor:   0.001 Pgp-substrate:   0.166
PAMPA:   0.976
?
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):   0.006
20% Bioavailability (F20%):   0.207 30% Bioavailability (F30%):   0.562
50% Bioavailability (F50%):   0.889

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.225 MRP1:   0.488
Plasma Protein Binding (PPB):   67.824% Volume Distribution (VD):   -0.517
Fu: 43.041%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.018
BSEP inhibitor:   0.689

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.314
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.016
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.176
CYP3A4-inhibitor:   0.023 CYP3A4-substrate:   0.787
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.985
HLM stability:   0.932
?
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):  3.619 Half-life (T1/2):  2.008

ADMET: Toxicity

hERG Blockers:  0.105 hERG Blockers (10um):  0.686
Human Hepatotoxicity (H-HT):  0.101 Drug-induced Liver Injury (DILI):  0.648
AMES Toxicity:  0.39 Rat Oral Acute Toxicity:  0.029
Maximum Recommended Daily Dose:  0.059 Skin Sensitization:  0.915
Carcinogencity:  0.313 Eye Corrosion:  0.001
Eye Irritation:  0.822 Respiratory Toxicity:  0.017
Drug-induced Neurotoxicity:  0.089 Ototoxicity:  0.407
Hematotoxicity:  0.012 Drug-induced Nephrotoxicity:  0.27
Genotoxicity:  0.032 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.176 Hek293 Cytotoxicity:  0.38
BCF:   0.75
?
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:   3.509
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.645
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.246
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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
NPO33462 flacourtia ramontchi Species Salicaceae Eukaryota n.a. n.a. n.a. PMID[22439591]

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
NPT2 Others Unspecified n.a. IC50 = 9300.0 nM PubChem BioAssay data set

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 NPC65833 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
0.7581 Intermediate Similarity NPC215811
0.7581 Intermediate Similarity NPC4958
0.6528 Remote Similarity NPC279281
0.6491 Remote Similarity NPC192229
0.6462 Remote Similarity NPC111785
0.6212 Remote Similarity NPC471345
0.6119 Remote Similarity NPC25389
0.6061 Remote Similarity NPC166277
0.6 Remote Similarity NPC36130
0.6 Remote Similarity NPC311803
0.6 Remote Similarity NPC132737
0.6 Remote Similarity NPC484156
0.597 Remote Similarity NPC472859
0.589 Remote Similarity NPC182350
0.589 Remote Similarity NPC289346
0.5873 Remote Similarity NPC57751
0.5833 Remote Similarity NPC102851
0.5802 Remote Similarity NPC231475
0.5797 Remote Similarity NPC119125
0.5781 Remote Similarity NPC198487
0.5775 Remote Similarity NPC471028
0.5753 Remote Similarity NPC5786
0.5738 Remote Similarity NPC114096
0.5732 Remote Similarity NPC474441
0.5658 Remote Similarity NPC479375
0.5606 Remote Similarity NPC233559
0.5571 Remote Similarity NPC90905
0.5556 Remote Similarity NPC327032
0.5507 Remote Similarity NPC140750
0.5493 Remote Similarity NPC93619
0.5441 Remote Similarity NPC4013
0.5439 Remote Similarity NPC142319
0.5429 Remote Similarity NPC1913
0.5417 Remote Similarity NPC160780
0.5373 Remote Similarity NPC479469
0.5352 Remote Similarity NPC92054
0.5342 Remote Similarity NPC197708
0.5303 Remote Similarity NPC148026
0.5238 Remote Similarity NPC129264
0.5205 Remote Similarity NPC320259
0.519 Remote Similarity NPC33298
0.5147 Remote Similarity NPC301857
0.5068 Remote Similarity NPC242756

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC65833 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