Natural Product: NPC152722

Natural Product IDNPC152722
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Leonuriside
IUPAC Name (2S,3R,4S,5S,6R)-2-(4-hydroxy-2,6-dimethoxyphenoxy)-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms leonuriside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464406
PubChem CID 14237626
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 NOQYJICHFNSIFZ-DIACKHNESA-N
Standard InCHI InChI=1S/C14H20O9/c1-20-7-3-6(16)4-8(21-2)13(7)23-14-12(19)11(18)10(17)9(5-15)22-14/h3-4,9-12,14-19H,5H2,1-2H3/t9-,10-,11+,12-,14+/m1/s1
SMILES OC[C@H]1O[C@@H](Oc2c(OC)cc(cc2OC)O)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   332.11 Volume:   304.79
?
Van der Waals volume.
Dense:   1.09 LogP:   -1.187
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.65
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.783
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   12.0
TPSA:   138.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.44 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.553 Fsp3:   0.571
MCE-18:   51.818
?
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:   0.461 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.199
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.073
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.251 Promiscuous compounds:   0.336

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.085 MDCK Permeability:   -5.122
Pgp-inhibitor:   0.0 Pgp-substrate:   0.174
PAMPA:   0.943
?
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):   0.066
20% Bioavailability (F20%):   0.039 30% Bioavailability (F30%):   0.409
50% Bioavailability (F50%):   0.884

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.613 MRP1:   0.264
Plasma Protein Binding (PPB):   65.807% Volume Distribution (VD):   -0.227
Fu: 33.079%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.02
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.014 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.667
HLM stability:   0.376
?
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):  3.326 Half-life (T1/2):  3.627

ADMET: Toxicity

hERG Blockers:  0.034 hERG Blockers (10um):  0.145
Human Hepatotoxicity (H-HT):  0.677 Drug-induced Liver Injury (DILI):  0.675
AMES Toxicity:  0.873 Rat Oral Acute Toxicity:  0.026
Maximum Recommended Daily Dose:  0.034 Skin Sensitization:  0.989
Carcinogencity:  0.412 Eye Corrosion:  0.001
Eye Irritation:  0.561 Respiratory Toxicity:  0.031
Drug-induced Neurotoxicity:  0.039 Ototoxicity:  0.853
Hematotoxicity:  0.343 Drug-induced Nephrotoxicity:  0.544
Genotoxicity:  0.286 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.118 Hek293 Cytotoxicity:  0.211
BCF:   0.27
?
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:   2.17
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.72
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.989
?
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
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. leaf n.a. PMID[17124632]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. fruit n.a. PMID[17124632]
NPO15741 Embelia ribes Species Primulaceae Eukaryota roots n.a. n.a. PMID[17125236]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[17125236]
NPO18521 Capparis flavicans Species Capparaceae Eukaryota aerial parts Khon Kaen Province, Thailand 2006-Aug PMID[19943620]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota Fruits n.a. n.a. PMID[31301930]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18521 Capparis flavicans Species Capparaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT81 Cell line A549 Homo sapiens IC50 > 10.0 ug.mL-1 PMID[17125236]
NPT179 Cell line A2780 Homo sapiens IC50 > 10.0 ug.mL-1 PMID[17125236]
NPT181 Cell line Bel-7402 Homo sapiens IC50 > 10.0 ug.mL-1 PMID[17125236]
NPT547 Cell line BGC-823 Homo sapiens IC50 > 10.0 ug.mL-1 PMID[17125236]
NPT180 Cell line HCT-8 Homo sapiens IC50 > 10.0 ug.mL-1 PMID[17125236]
NPT83 Cell line MCF7 Homo sapiens Activity < 0.1 uM PMID[19943620]
NPT83 Cell line MCF7 Homo sapiens Activity > 100.0 uM PMID[19943620]
NPT396 Cell line T47D Homo sapiens Activity = 0.4 uM PMID[19943620]
NPT396 Cell line T47D Homo sapiens Activity = 39.0 uM PMID[19943620]
NPT396 Cell line T47D Homo sapiens Activity > 100.0 uM PMID[19943620]
NPT113 Cell line RAW264.7 Mus musculus IC50 > 50000.0 nM PMID[31301930]

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 NPC152722 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
0.7333 Intermediate Similarity NPC217854
0.6875 Remote Similarity NPC299144
0.6739 Remote Similarity NPC276195
0.66 Remote Similarity NPC69513
0.66 Remote Similarity NPC145900
0.6471 Remote Similarity NPC48863
0.6471 Remote Similarity NPC95292
0.6471 Remote Similarity NPC251981
0.6471 Remote Similarity NPC13745
0.6458 Remote Similarity NPC192810
0.6383 Remote Similarity NPC142319
0.6346 Remote Similarity NPC215833
0.625 Remote Similarity NPC484157
0.6226 Remote Similarity NPC49074
0.6222 Remote Similarity NPC228907
0.6122 Remote Similarity NPC153149
0.6111 Remote Similarity NPC162093
0.6111 Remote Similarity NPC23084
0.6078 Remote Similarity NPC12308
0.6038 Remote Similarity NPC40377
0.6 Remote Similarity NPC25817
0.6 Remote Similarity NPC210478
0.5962 Remote Similarity NPC221090
0.5789 Remote Similarity NPC95392
0.5789 Remote Similarity NPC84013
0.5789 Remote Similarity NPC55715
0.5789 Remote Similarity NPC106025
0.5789 Remote Similarity NPC35877
0.5741 Remote Similarity NPC310661
0.569 Remote Similarity NPC232673
0.5686 Remote Similarity NPC9248
0.5645 Remote Similarity NPC216129
0.5645 Remote Similarity NPC130449
0.5645 Remote Similarity NPC99233
0.5645 Remote Similarity NPC248132
0.5636 Remote Similarity NPC218685
0.5593 Remote Similarity NPC199335
0.5593 Remote Similarity NPC470236
0.5593 Remote Similarity NPC477240
0.5574 Remote Similarity NPC60756
0.5574 Remote Similarity NPC604892
0.5556 Remote Similarity NPC214454
0.5556 Remote Similarity NPC166040
0.5556 Remote Similarity NPC606849
0.55 Remote Similarity NPC294166
0.55 Remote Similarity NPC190217
0.55 Remote Similarity NPC115022
0.5472 Remote Similarity NPC226712
0.5472 Remote Similarity NPC608788
0.5439 Remote Similarity NPC26653
0.5439 Remote Similarity NPC80600
0.5424 Remote Similarity NPC97326
0.541 Remote Similarity NPC604095
0.54 Remote Similarity NPC212729
0.54 Remote Similarity NPC604498
0.5345 Remote Similarity NPC473044
0.5345 Remote Similarity NPC479029
0.5323 Remote Similarity NPC260681
0.5312 Remote Similarity NPC148273
0.5312 Remote Similarity NPC30432
0.5312 Remote Similarity NPC601828
0.5303 Remote Similarity NPC51328
0.5303 Remote Similarity NPC55158
0.5294 Remote Similarity NPC269242
0.5294 Remote Similarity NPC5778
0.5283 Remote Similarity NPC609376
0.5273 Remote Similarity NPC166168
0.5273 Remote Similarity NPC604209
0.5263 Remote Similarity NPC472024
0.5263 Remote Similarity NPC270849
0.5254 Remote Similarity NPC25292
0.5238 Remote Similarity NPC98777
0.5238 Remote Similarity NPC210192
0.5238 Remote Similarity NPC189115
0.5238 Remote Similarity NPC212770
0.5238 Remote Similarity NPC475096
0.5238 Remote Similarity NPC475084
0.5231 Remote Similarity NPC299435
0.5231 Remote Similarity NPC169248
0.5231 Remote Similarity NPC72649
0.5224 Remote Similarity NPC106625
0.5217 Remote Similarity NPC472381
0.5192 Remote Similarity NPC294470
0.5172 Remote Similarity NPC214910
0.5172 Remote Similarity NPC26080
0.5172 Remote Similarity NPC165686
0.5167 Remote Similarity NPC85799
0.5167 Remote Similarity NPC473045
0.5167 Remote Similarity NPC303422
0.5167 Remote Similarity NPC218003
0.5167 Remote Similarity NPC34456
0.5161 Remote Similarity NPC479030
0.5161 Remote Similarity NPC185778
0.5152 Remote Similarity NPC479692
0.5085 Remote Similarity NPC248355
0.5085 Remote Similarity NPC105827
0.5082 Remote Similarity NPC478871
0.5082 Remote Similarity NPC190714
0.5082 Remote Similarity NPC478870
0.5082 Remote Similarity NPC99515
0.5082 Remote Similarity NPC478872
0.5082 Remote Similarity NPC475628
0.5082 Remote Similarity NPC478873
0.5082 Remote Similarity NPC605646
0.5079 Remote Similarity NPC600107
0.5077 Remote Similarity NPC479447
0.5077 Remote Similarity NPC271385
0.5077 Remote Similarity NPC605700
0.5075 Remote Similarity NPC61594
0.5075 Remote Similarity NPC260604

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC152722 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
0.5472 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