Natural Product: NPC548243

Natural Product IDNPC548243
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{S},3~{R},4~{R},5~{S})-2-(hydroxymethyl)-6-(3,4,5-trimethoxyphenoxy)tetrahydropyran-3,4,5-triol
IUPAC Name (2~{S},3~{R},4~{R},5~{S})-2-(hydroxymethyl)-6-(3,4,5-trimethoxyphenoxy)tetrahydropyran-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 NBLLRWANAFOKON-HXMBFPRCSA-N
Standard InCHI InChI=1S/C15H22O9/c1-20-8-4-7(5-9(21-2)14(8)22-3)23-15-13(19)12(18)11(17)10(6-16)24-15/h4-5,10-13,15-19H,6H2,1-3H3/t10-,11-,12+,13-,15?/m0/s1
SMILES COC1=CC(OC2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)=CC(OC)=C1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.13 Volume:   322.086
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Van der Waals volume.
Dense:   1.075 LogP:   -0.639
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.402
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.095
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   12.0
TPSA:   127.07
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Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.507 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.417 Fsp3:   0.6
MCE-18:   51.25
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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:   0.38 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.064
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.036
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.245 Promiscuous compounds:   0.07

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.063 MDCK Permeability:   -5.202
Pgp-inhibitor:   0.003 Pgp-substrate:   0.288
PAMPA:   0.742
?
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):   0.758
20% Bioavailability (F20%):   0.181 30% Bioavailability (F30%):   0.606
50% Bioavailability (F50%):   0.886

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.492 MRP1:   0.636
Plasma Protein Binding (PPB):   65.073% Volume Distribution (VD):   -0.154
Fu: 32.917%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.981
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.425
BSEP inhibitor:   0.12

ADMET: Metabolism

CYP1A2-inhibitor:   0.062 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.359 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.023 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.031
CYP3A4-inhibitor:   0.581 CYP3A4-substrate:   0.578
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.074
HLM stability:   0.025
?
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):  1.917 Half-life (T1/2):  2.378

ADMET: Toxicity

hERG Blockers:  0.025 hERG Blockers (10um):  0.264
Human Hepatotoxicity (H-HT):  0.474 Drug-induced Liver Injury (DILI):  0.605
AMES Toxicity:  0.689 Rat Oral Acute Toxicity:  0.063
Maximum Recommended Daily Dose:  0.017 Skin Sensitization:  0.944
Carcinogencity:  0.2 Eye Corrosion:  0.003
Eye Irritation:  0.654 Respiratory Toxicity:  0.046
Drug-induced Neurotoxicity:  0.068 Ototoxicity:  0.675
Hematotoxicity:  0.328 Drug-induced Nephrotoxicity:  0.702
Genotoxicity:  0.026 RPMI-8226 Immunitoxicity:  0.157
A549 Cytotoxicity:  0.136 Hek293 Cytotoxicity:  0.088
BCF:   0.371
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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:   2.456
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.952
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.192
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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
NPO46472 Salsola tetrandra Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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

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 NPC548243 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
1.0 High Similarity NPC276195
0.9231 High Similarity NPC217854
0.7674 Intermediate Similarity NPC153149
0.75 Intermediate Similarity NPC25817
0.7273 Intermediate Similarity NPC192810
0.7021 Intermediate Similarity NPC145900
0.6739 Remote Similarity NPC152722
0.6667 Remote Similarity NPC228907
0.6596 Remote Similarity NPC299144
0.6444 Remote Similarity NPC142319
0.6327 Remote Similarity NPC221090
0.6327 Remote Similarity NPC69513
0.6275 Remote Similarity NPC218685
0.62 Remote Similarity NPC48863
0.62 Remote Similarity NPC95292
0.62 Remote Similarity NPC251981
0.62 Remote Similarity NPC13745
0.6154 Remote Similarity NPC23084
0.6111 Remote Similarity NPC104167
0.6087 Remote Similarity NPC212729
0.6087 Remote Similarity NPC604498
0.6078 Remote Similarity NPC215833
0.6 Remote Similarity NPC247146
0.5965 Remote Similarity NPC479030
0.5962 Remote Similarity NPC49074
0.5957 Remote Similarity NPC269242
0.5926 Remote Similarity NPC479029
0.5926 Remote Similarity NPC607702
0.5918 Remote Similarity NPC609376
0.5882 Remote Similarity NPC166040
0.5849 Remote Similarity NPC162093
0.5849 Remote Similarity NPC479028
0.5849 Remote Similarity NPC479031
0.5833 Remote Similarity NPC294470
0.5741 Remote Similarity NPC210478
0.5714 Remote Similarity NPC171533
0.5714 Remote Similarity NPC232673
0.5636 Remote Similarity NPC473044
0.5625 Remote Similarity NPC484157
0.56 Remote Similarity NPC60589
0.56 Remote Similarity NPC469708
0.56 Remote Similarity NPC604439
0.5556 Remote Similarity NPC472024
0.5556 Remote Similarity NPC270849
0.5536 Remote Similarity NPC95392
0.5536 Remote Similarity NPC84013
0.5536 Remote Similarity NPC55715
0.5536 Remote Similarity NPC35877
0.5536 Remote Similarity NPC189589
0.549 Remote Similarity NPC200092
0.549 Remote Similarity NPC12308
0.549 Remote Similarity NPC226712
0.549 Remote Similarity NPC608788
0.5455 Remote Similarity NPC26653
0.5455 Remote Similarity NPC214910
0.5455 Remote Similarity NPC80600
0.5439 Remote Similarity NPC473045
0.5439 Remote Similarity NPC208769
0.541 Remote Similarity NPC99233
0.54 Remote Similarity NPC9248
0.5385 Remote Similarity NPC80098
0.5357 Remote Similarity NPC248355
0.5345 Remote Similarity NPC470236
0.5333 Remote Similarity NPC604892
0.5323 Remote Similarity NPC148273
0.5294 Remote Similarity NPC190730
0.5283 Remote Similarity NPC214454
0.5273 Remote Similarity NPC604356
0.5273 Remote Similarity NPC606892
0.5263 Remote Similarity NPC55040
0.5246 Remote Similarity NPC475096
0.5246 Remote Similarity NPC475084
0.5185 Remote Similarity NPC40377
0.5185 Remote Similarity NPC310661
0.5185 Remote Similarity NPC9912
0.5179 Remote Similarity NPC164599
0.5172 Remote Similarity NPC302378
0.5172 Remote Similarity NPC604162
0.5167 Remote Similarity NPC37468
0.5167 Remote Similarity NPC486107
0.5088 Remote Similarity NPC105827
0.5082 Remote Similarity NPC146803
0.5082 Remote Similarity NPC166277
0.5079 Remote Similarity NPC486104
0.5079 Remote Similarity NPC486102
0.5079 Remote Similarity NPC606849
0.5075 Remote Similarity NPC110349

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC548243 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
0.549 Remote Similarity NPD1091 Pre-clinical

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