Natural Product: NPC23134

Natural Product IDNPC23134
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isopropyl O-Beta-D-Glucopyranoside
IUPAC Name (2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-propan-2-yloxyoxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3326714
PubChem CID 21572943
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:0002207] O-glycosyl 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 UOEFDXYUEPHESS-SYHAXYEDSA-N
Standard InCHI InChI=1S/C9H18O6/c1-4(2)14-9-8(13)7(12)6(11)5(3-10)15-9/h4-13H,3H2,1-2H3/t5-,6-,7+,8-,9-/m1/s1
SMILES OC[C@H]1O[C@@H](OC(C)C)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   222.11 Volume:   208.405
?
Van der Waals volume.
Dense:   1.066 LogP:   -0.616
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.389
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.563
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 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:   0.45 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.627 Fsp3:   1.0
MCE-18:   23.0
?
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:   0.14 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.031
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.497 Promiscuous compounds:   0.006

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.796 MDCK Permeability:   -4.852
Pgp-inhibitor:   0.001 Pgp-substrate:   0.3
PAMPA:   0.907
?
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):   0.337
20% Bioavailability (F20%):   0.035 30% Bioavailability (F30%):   0.663
50% Bioavailability (F50%):   0.688

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.687 MRP1:   0.236
Plasma Protein Binding (PPB):   28.038% Volume Distribution (VD):   -0.572
Fu: 78.641%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.934
OATP1B3 inhibitor:   0.979 BCRP inhibitor:   0.092
BSEP inhibitor:   0.003

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.112 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.386
HLM stability:   0.321
?
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):  3.291 Half-life (T1/2):  2.718

ADMET: Toxicity

hERG Blockers:  0.025 hERG Blockers (10um):  0.126
Human Hepatotoxicity (H-HT):  0.58 Drug-induced Liver Injury (DILI):  0.746
AMES Toxicity:  0.887 Rat Oral Acute Toxicity:  0.029
Maximum Recommended Daily Dose:  0.013 Skin Sensitization:  0.993
Carcinogencity:  0.294 Eye Corrosion:  0.027
Eye Irritation:  0.848 Respiratory Toxicity:  0.026
Drug-induced Neurotoxicity:  0.05 Ototoxicity:  0.853
Hematotoxicity:  0.439 Drug-induced Nephrotoxicity:  0.613
Genotoxicity:  0.096 RPMI-8226 Immunitoxicity:  0.077
A549 Cytotoxicity:  0.12 Hek293 Cytotoxicity:  0.085
BCF:   0.344
?
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:   1.984
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.246
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.565
?
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
NPO30686 Citrus hystrix Species Rutaceae Eukaryota n.a. exocarp n.a. PMID[20964319]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota Fruits n.a. n.a. PMID[23506561]
NPO8874 Glehnia littoralis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[24813739]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota leaves n.a. n.a. PMID[25127165]
NPO30686 Citrus hystrix Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[38067483]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8874 Glehnia littoralis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30686 Citrus hystrix Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8874 Glehnia littoralis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8874 Glehnia littoralis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8874 Glehnia littoralis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8874 Glehnia littoralis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8874 Glehnia littoralis Species Apiaceae 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 = 7.31 % PMID[25127165]

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 = 0.22 uM PMID[25127165]
NPT35 Others n.a. n.a. Activity = 1.79 uM PMID[25127165]

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 NPC23134 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
0.8077 Intermediate Similarity NPC42503
0.8077 Intermediate Similarity NPC282143
0.8077 Intermediate Similarity NPC299781
0.8077 Intermediate Similarity NPC157193
0.8077 Intermediate Similarity NPC608193
0.7407 Intermediate Similarity NPC107914
0.7407 Intermediate Similarity NPC242073
0.7241 Intermediate Similarity NPC124963
0.6562 Remote Similarity NPC143326
0.6452 Remote Similarity NPC326533
0.6364 Remote Similarity NPC31496
0.625 Remote Similarity NPC317501
0.625 Remote Similarity NPC605930
0.6176 Remote Similarity NPC233726
0.6111 Remote Similarity NPC246558
0.6111 Remote Similarity NPC67660
0.6111 Remote Similarity NPC165198
0.6111 Remote Similarity NPC209753
0.6111 Remote Similarity NPC58629
0.5833 Remote Similarity NPC155457
0.5833 Remote Similarity NPC268243
0.5676 Remote Similarity NPC323361
0.5556 Remote Similarity NPC130683
0.5526 Remote Similarity NPC13143
0.5526 Remote Similarity NPC290179
0.5526 Remote Similarity NPC132938
0.5526 Remote Similarity NPC294813
0.5526 Remote Similarity NPC606861
0.5526 Remote Similarity NPC607126
0.55 Remote Similarity NPC317023
0.55 Remote Similarity NPC482639
0.55 Remote Similarity NPC489878
0.5385 Remote Similarity NPC32148
0.5385 Remote Similarity NPC83248
0.5263 Remote Similarity NPC145112
0.525 Remote Similarity NPC89145
0.525 Remote Similarity NPC157514
0.525 Remote Similarity NPC322314
0.525 Remote Similarity NPC269166
0.5238 Remote Similarity NPC472174
0.5238 Remote Similarity NPC477750
0.5238 Remote Similarity NPC477763
0.5238 Remote Similarity NPC477757
0.5238 Remote Similarity NPC477762
0.5238 Remote Similarity NPC477755
0.5238 Remote Similarity NPC477753
0.5128 Remote Similarity NPC603514
0.5122 Remote Similarity NPC601741
0.5116 Remote Similarity NPC16090

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC23134 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
0.6562 Remote Similarity NPD905 Phase 4
0.6207 Remote Similarity NPD8994 Approved
0.6111 Remote Similarity NPD888 Phase 3
0.6111 Remote Similarity NPD890 Clinical (unspecified phase)
0.6111 Remote Similarity NPD891 Phase 3
0.6111 Remote Similarity NPD892 Phase 3
0.6111 Remote Similarity NPD893 Approved
0.5714 Remote Similarity NPD904 Phase 3
0.5676 Remote Similarity NPD889 Approved
0.5676 Remote Similarity NPD894 Phase 4
0.5556 Remote Similarity NPD887 Approved
0.5556 Remote Similarity NPD895 Phase 4

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