Natural Product: NPC215811

Natural Product IDNPC215811
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Flacourtoside B
IUPAC Name [(2R,3S,4S,5R,6S)-6-(2-formyl-4-hydroxyphenoxy)-3,4,5-trihydroxyoxan-2-yl]methyl benzoate
Synonyms Flacourtoside B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2036484
PubChem CID 57409244
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 SSJSZNSQHPLDCR-BFMVXSJESA-N
Standard InCHI InChI=1S/C20H20O9/c21-9-12-8-13(22)6-7-14(12)28-20-18(25)17(24)16(23)15(29-20)10-27-19(26)11-4-2-1-3-5-11/h1-9,15-18,20,22-25H,10H2/t15-,16-,17+,18-,20-/m1/s1
SMILES c1ccc(cc1)C(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@H](Oc2ccc(cc2C=O)O)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   404.11 Volume:   386.827
?
Van der Waals volume.
Dense:   1.045 LogP:   1.138
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.308
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.234
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   142.75
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Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.393 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.572 Fsp3:   0.3
MCE-18:   64.308
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.51 Fluc inhibitor:   0.145
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.17
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.373
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.257 Promiscuous compounds:   0.244

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.947 MDCK Permeability:   -5.021
Pgp-inhibitor:   0.002 Pgp-substrate:   0.01
PAMPA:   0.981
?
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):   0.03
20% Bioavailability (F20%):   0.079 30% Bioavailability (F30%):   0.538
50% Bioavailability (F50%):   0.591

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.263 MRP1:   0.149
Plasma Protein Binding (PPB):   81.845% Volume Distribution (VD):   -0.519
Fu: 22.387%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.001
BSEP inhibitor:   0.136

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.006
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.985
HLM stability:   0.171
?
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):  3.637 Half-life (T1/2):  2.713

ADMET: Toxicity

hERG Blockers:  0.078 hERG Blockers (10um):  0.52
Human Hepatotoxicity (H-HT):  0.103 Drug-induced Liver Injury (DILI):  0.671
AMES Toxicity:  0.583 Rat Oral Acute Toxicity:  0.014
Maximum Recommended Daily Dose:  0.092 Skin Sensitization:  0.952
Carcinogencity:  0.446 Eye Corrosion:  0.0
Eye Irritation:  0.78 Respiratory Toxicity:  0.015
Drug-induced Neurotoxicity:  0.053 Ototoxicity:  0.577
Hematotoxicity:  0.021 Drug-induced Nephrotoxicity:  0.175
Genotoxicity:  0.125 RPMI-8226 Immunitoxicity:  0.065
A549 Cytotoxicity:  0.137 Hek293 Cytotoxicity:  0.444
BCF:   0.553
?
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:   3.387
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.631
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.139
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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 = 71100.0 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 NPC215811 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
0.8125 Intermediate Similarity NPC4958
0.7887 Intermediate Similarity NPC132737
0.7581 Intermediate Similarity NPC65833
0.7027 Intermediate Similarity NPC279281
0.6265 Remote Similarity NPC231475
0.619 Remote Similarity NPC474441
0.6056 Remote Similarity NPC111785
0.5811 Remote Similarity NPC93619
0.5676 Remote Similarity NPC92054
0.5634 Remote Similarity NPC484156
0.5541 Remote Similarity NPC1913
0.5513 Remote Similarity NPC102851
0.5479 Remote Similarity NPC166277
0.5455 Remote Similarity NPC36130
0.5455 Remote Similarity NPC311803
0.5405 Remote Similarity NPC471345
0.5375 Remote Similarity NPC289346
0.5333 Remote Similarity NPC25389
0.5325 Remote Similarity NPC160780
0.5306 Remote Similarity NPC475174
0.5263 Remote Similarity NPC119125
0.5256 Remote Similarity NPC327032
0.52 Remote Similarity NPC472859
0.5181 Remote Similarity NPC479375
0.5147 Remote Similarity NPC114096
0.5119 Remote Similarity NPC478797
0.5063 Remote Similarity NPC197708
0.5062 Remote Similarity NPC5786

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC215811 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