Natural Product: NPC233726

Natural Product IDNPC233726
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 N-Butyl O-Beta-D-Glucopyranoside
IUPAC Name (2R,3R,4S,5S,6R)-2-butoxy-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3326716
PubChem CID 111068
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001766] Fatty acyl glycosides
          • [CHEMONTID:0003861] Fatty acyl glycosides of mono- and disaccharides

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 BZANQLIRVMZFOS-HOTMZDKISA-N
Standard InCHI InChI=1S/C10H20O6/c1-2-3-4-15-10-9(14)8(13)7(12)6(5-11)16-10/h6-14H,2-5H2,1H3/t6-,7-,8+,9-,10-/m1/s1
SMILES CCCCO[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   236.13 Volume:   225.701
?
Van der Waals volume.
Dense:   1.046 LogP:   -0.318
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.053
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.036
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   6.0
TPSA:   99.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   1.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.438 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.444 Fsp3:   1.0
MCE-18:   20.0
?
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:   0.281 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.036
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.454 Promiscuous compounds:   0.005

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.71 MDCK Permeability:   -4.929
Pgp-inhibitor:   0.004 Pgp-substrate:   0.525
PAMPA:   0.905
?
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):   0.831
20% Bioavailability (F20%):   0.176 30% Bioavailability (F30%):   0.951
50% Bioavailability (F50%):   0.682

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.253 MRP1:   0.237
Plasma Protein Binding (PPB):   66.511% Volume Distribution (VD):   -0.283
Fu: 32.871%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.058
BSEP inhibitor:   0.01

ADMET: Metabolism

CYP1A2-inhibitor:   0.759 CYP1A2-substrate:   0.006
CYP2C19-inhibitor:   0.84 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.42 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.013 CYP3A4-substrate:   0.175
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.221
HLM stability:   0.688
?
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):  3.814 Half-life (T1/2):  2.156

ADMET: Toxicity

hERG Blockers:  0.034 hERG Blockers (10um):  0.195
Human Hepatotoxicity (H-HT):  0.423 Drug-induced Liver Injury (DILI):  0.594
AMES Toxicity:  0.791 Rat Oral Acute Toxicity:  0.043
Maximum Recommended Daily Dose:  0.012 Skin Sensitization:  0.992
Carcinogencity:  0.241 Eye Corrosion:  0.063
Eye Irritation:  0.811 Respiratory Toxicity:  0.053
Drug-induced Neurotoxicity:  0.024 Ototoxicity:  0.846
Hematotoxicity:  0.37 Drug-induced Nephrotoxicity:  0.488
Genotoxicity:  0.007 RPMI-8226 Immunitoxicity:  0.067
A549 Cytotoxicity:  0.235 Hek293 Cytotoxicity:  0.117
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:   2.369
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.503
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.956
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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
NPO6648 Piper retrofractum Species Piperaceae Eukaryota Fruits n.a. n.a. PMID[23506561]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota leaves n.a. n.a. PMID[25127165]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6648 Piper retrofractum Species Piperaceae 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 Inhibition = 9.75 % PMID[9358638]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT35 Others n.a. n.a. Activity = 0.62 uM Open TG-GATES in vivo data: Hematology
NPT35 Others n.a. n.a. Activity = 3.64 uM PMID[24428261]

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 NPC233726 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
0.8333 Intermediate Similarity NPC606861
0.8333 Intermediate Similarity NPC607126
0.7297 Intermediate Similarity NPC155457
0.7273 Intermediate Similarity NPC124963
0.6923 Remote Similarity NPC13143
0.6923 Remote Similarity NPC294813
0.6744 Remote Similarity NPC277570
0.6571 Remote Similarity NPC326533
0.6176 Remote Similarity NPC23134
0.6136 Remote Similarity NPC147292
0.5882 Remote Similarity NPC42503
0.5882 Remote Similarity NPC282143
0.5882 Remote Similarity NPC107914
0.5882 Remote Similarity NPC242073
0.5882 Remote Similarity NPC299781
0.5882 Remote Similarity NPC157193
0.5882 Remote Similarity NPC608193
0.561 Remote Similarity NPC268243
0.5532 Remote Similarity NPC206601
0.551 Remote Similarity NPC280367
0.5476 Remote Similarity NPC145112
0.54 Remote Similarity NPC488690
0.5385 Remote Similarity NPC143326
0.5319 Remote Similarity NPC63058
0.5306 Remote Similarity NPC471879
0.5306 Remote Similarity NPC12040
0.525 Remote Similarity NPC31496
0.5217 Remote Similarity NPC36927
0.5217 Remote Similarity NPC271772
0.52 Remote Similarity NPC285003
0.52 Remote Similarity NPC470124
0.5128 Remote Similarity NPC317501
0.5128 Remote Similarity NPC605930
0.5111 Remote Similarity NPC89145
0.5111 Remote Similarity NPC157514
0.5111 Remote Similarity NPC322314
0.5111 Remote Similarity NPC269166
0.5088 Remote Similarity NPC603467
0.5088 Remote Similarity NPC606101

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC233726 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
0.5897 Remote Similarity NPD904 Phase 3

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