Natural Product: NPC162093

Natural Product IDNPC162093
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methylsyringin
IUPAC Name (2S,3R,4S,5S,6R)-2-[2,6-dimethoxy-4-[(E)-3-methoxyprop-1-enyl]phenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3236505
PubChem CID 15108321
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 KDZYNPVXUQIVAO-LSUNSJSKSA-N
Standard InCHI InChI=1S/C18H26O9/c1-23-6-4-5-10-7-11(24-2)17(12(8-10)25-3)27-18-16(22)15(21)14(20)13(9-19)26-18/h4-5,7-8,13-16,18-22H,6,9H2,1-3H3/b5-4+/t13-,14-,15+,16-,18+/m1/s1
SMILES COC/C=C/c1cc(c(c(c1)OC)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.16 Volume:   371.337
?
Van der Waals volume.
Dense:   1.04 LogP:   -0.286
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.411
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.669
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   13.0
TPSA:   127.07
?
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:   0.469 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.748 Fsp3:   0.556
MCE-18:   50.357
?
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:   0.407 Fluc inhibitor:   0.316
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.194
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.238
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.2 Promiscuous compounds:   0.079

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.375 MDCK Permeability:   -4.829
Pgp-inhibitor:   0.001 Pgp-substrate:   0.165
PAMPA:   0.838
?
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):   0.405
20% Bioavailability (F20%):   0.125 30% Bioavailability (F30%):   0.76
50% Bioavailability (F50%):   0.894

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.418 MRP1:   0.134
Plasma Protein Binding (PPB):   73.457% Volume Distribution (VD):   -0.27
Fu: 27.47%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.24
BSEP inhibitor:   0.034

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.017 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.034
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.014
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.468
HLM stability:   0.278
?
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):  2.957 Half-life (T1/2):  2.545

ADMET: Toxicity

hERG Blockers:  0.044 hERG Blockers (10um):  0.136
Human Hepatotoxicity (H-HT):  0.679 Drug-induced Liver Injury (DILI):  0.616
AMES Toxicity:  0.857 Rat Oral Acute Toxicity:  0.021
Maximum Recommended Daily Dose:  0.027 Skin Sensitization:  0.991
Carcinogencity:  0.366 Eye Corrosion:  0.0
Eye Irritation:  0.11 Respiratory Toxicity:  0.016
Drug-induced Neurotoxicity:  0.039 Ototoxicity:  0.928
Hematotoxicity:  0.511 Drug-induced Nephrotoxicity:  0.821
Genotoxicity:  0.048 RPMI-8226 Immunitoxicity:  0.105
A549 Cytotoxicity:  0.091 Hek293 Cytotoxicity:  0.139
BCF:   0.535
?
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:   2.905
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.622
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.575
?
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
NPO19294 Acalypha communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[12088430]
NPO15805 Didymochlaena truncatula Species Didymochlaenaceae Eukaryota n.a. n.a. n.a. PMID[16499333]
NPO18571 Drypetes roxburghii Species Putranjivaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5731 Euphorbia humifusa Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2922 Botryosphaeria berengeriana Species Botryosphaeriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5731 Euphorbia humifusa Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5731 Euphorbia humifusa Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5731 Euphorbia humifusa Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20917 Crotalaria globifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20858 Rosa acuminata Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17198 Melicope mantellii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15805 Didymochlaena truncatula Species Didymochlaenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8757 Protaminobacter ruber Species n.a. Bacteria n.a. n.a. n.a. Database[UNPD]
NPO17976 Osteospermum caulescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19294 Acalypha communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18571 Drypetes roxburghii Species Putranjivaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20594 Latrunculia oparinae Species Latrunculiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2922 Botryosphaeria berengeriana Species Botryosphaeriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5731 Euphorbia humifusa Species Euphorbiaceae 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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 17200.0 nM PMID[24679441]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 17500.0 nM PMID[24679441]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 30.0 % PMID[24679441]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 21.5 % PMID[24679441]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 14600.0 nM PMID[34658231]
NPT113 Cell line RAW264.7 Mus musculus Activity n.a. n.a. n.a. PMID[34658231]

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 NPC162093 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
0.8679 High Similarity NPC470236
0.8235 Intermediate Similarity NPC49074
0.7925 Intermediate Similarity NPC210478
0.7818 Intermediate Similarity NPC302378
0.7193 Intermediate Similarity NPC232673
0.6923 Remote Similarity NPC299144
0.6667 Remote Similarity NPC69513
0.6545 Remote Similarity NPC48863
0.6545 Remote Similarity NPC251981
0.6545 Remote Similarity NPC13745
0.6452 Remote Similarity NPC164857
0.6429 Remote Similarity NPC215833
0.6346 Remote Similarity NPC217854
0.6271 Remote Similarity NPC248355
0.6271 Remote Similarity NPC479029
0.625 Remote Similarity NPC479448
0.6167 Remote Similarity NPC95392
0.6167 Remote Similarity NPC84013
0.6167 Remote Similarity NPC55715
0.6167 Remote Similarity NPC55040
0.6167 Remote Similarity NPC35877
0.6111 Remote Similarity NPC152722
0.6032 Remote Similarity NPC479030
0.5849 Remote Similarity NPC276195
0.5833 Remote Similarity NPC132895
0.5781 Remote Similarity NPC37468
0.569 Remote Similarity NPC95292
0.5645 Remote Similarity NPC104167
0.5614 Remote Similarity NPC200092
0.5606 Remote Similarity NPC475084
0.5522 Remote Similarity NPC216129
0.5522 Remote Similarity NPC130449
0.5522 Remote Similarity NPC248132
0.5469 Remote Similarity NPC307110
0.5455 Remote Similarity NPC474044
0.5429 Remote Similarity NPC51328
0.5429 Remote Similarity NPC55158
0.5424 Remote Similarity NPC166040
0.541 Remote Similarity NPC479028
0.541 Remote Similarity NPC270849
0.541 Remote Similarity NPC479031
0.541 Remote Similarity NPC604356
0.5385 Remote Similarity NPC228907
0.5357 Remote Similarity NPC153149
0.5345 Remote Similarity NPC608788
0.5342 Remote Similarity NPC270751
0.5303 Remote Similarity NPC486107
0.5303 Remote Similarity NPC604095
0.5263 Remote Similarity NPC25817
0.5246 Remote Similarity NPC218685
0.5217 Remote Similarity NPC479447
0.5217 Remote Similarity NPC486102
0.52 Remote Similarity NPC478701
0.519 Remote Similarity NPC269559
0.5161 Remote Similarity NPC472024
0.5161 Remote Similarity NPC251102
0.5161 Remote Similarity NPC210298
0.5088 Remote Similarity NPC192810
0.5085 Remote Similarity NPC226712
0.5082 Remote Similarity NPC9912
0.5079 Remote Similarity NPC26653
0.5079 Remote Similarity NPC80600
0.5079 Remote Similarity NPC481303
0.5075 Remote Similarity NPC185778
0.5067 Remote Similarity NPC93924

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC162093 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
0.5085 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