Natural Product: NPC55040

Natural Product IDNPC55040
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Coniferyaldehyde Glucoside
IUPAC Name (E)-3-[3-methoxy-4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]prop-2-enal
Synonyms Coniferyaldehyde Glucoside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1911058
PubChem CID 15699109
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 PJFKUPRDDXTASO-FAOXUISGSA-N
Standard InCHI InChI=1S/C16H20O8/c1-22-11-7-9(3-2-6-17)4-5-10(11)23-16-15(21)14(20)13(19)12(8-18)24-16/h2-7,12-16,18-21H,8H2,1H3/b3-2+/t12-,13-,14+,15-,16-/m1/s1
SMILES O=C/C=C/c1ccc(c(c1)OC)O[C@@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.12 Volume:   325.319
?
Van der Waals volume.
Dense:   1.045 LogP:   -0.262
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.366
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.558
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   14.0
TPSA:   125.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.387 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.687 Fsp3:   0.438
MCE-18:   48.087
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.608 Fluc inhibitor:   0.636
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.231
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.149
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.264 Promiscuous compounds:   0.052

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.465 MDCK Permeability:   -5.1
Pgp-inhibitor:   0.035 Pgp-substrate:   0.045
PAMPA:   0.807
?
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):   0.786
20% Bioavailability (F20%):   0.607 30% Bioavailability (F30%):   0.965
50% Bioavailability (F50%):   0.952

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.002
Plasma Protein Binding (PPB):   72.656% Volume Distribution (VD):   -0.598
Fu: 28.195%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.676
BSEP inhibitor:   0.452

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.01
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.454
HLM stability:   0.034
?
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):  2.696 Half-life (T1/2):  2.727

ADMET: Toxicity

hERG Blockers:  0.039 hERG Blockers (10um):  0.099
Human Hepatotoxicity (H-HT):  0.703 Drug-induced Liver Injury (DILI):  0.849
AMES Toxicity:  0.953 Rat Oral Acute Toxicity:  0.046
Maximum Recommended Daily Dose:  0.03 Skin Sensitization:  0.994
Carcinogencity:  0.353 Eye Corrosion:  0.0
Eye Irritation:  0.475 Respiratory Toxicity:  0.026
Drug-induced Neurotoxicity:  0.079 Ototoxicity:  0.862
Hematotoxicity:  0.318 Drug-induced Nephrotoxicity:  0.766
Genotoxicity:  0.679 RPMI-8226 Immunitoxicity:  0.098
A549 Cytotoxicity:  0.112 Hek293 Cytotoxicity:  0.104
BCF:   0.761
?
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:   3.359
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.159
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.431
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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
NPO16259 Syringa reticulata Species Oleaceae Eukaryota n.a. n.a. n.a. PMID[21955940]
NPO16259 Syringa reticulata Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16259 Syringa reticulata Species Oleaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC50 > 100000.0 nM PMID[21955940]
NPT1 Others Radical scavenging activity n.a. EC50 > 100000.0 nM PMID[10691710]

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 NPC55040 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 NPC248355
0.8036 Intermediate Similarity NPC302378
0.7818 Intermediate Similarity NPC210478
0.7333 Intermediate Similarity NPC37468
0.6786 Remote Similarity NPC166040
0.678 Remote Similarity NPC479029
0.6774 Remote Similarity NPC604095
0.6724 Remote Similarity NPC270849
0.6441 Remote Similarity NPC472024
0.6338 Remote Similarity NPC93924
0.6333 Remote Similarity NPC26653
0.6333 Remote Similarity NPC80600
0.6271 Remote Similarity NPC49074
0.6167 Remote Similarity NPC162093
0.6167 Remote Similarity NPC479028
0.6167 Remote Similarity NPC479031
0.614 Remote Similarity NPC200092
0.6102 Remote Similarity NPC9912
0.6053 Remote Similarity NPC478985
0.5962 Remote Similarity NPC228907
0.5902 Remote Similarity NPC604356
0.5846 Remote Similarity NPC276753
0.5846 Remote Similarity NPC205796
0.5811 Remote Similarity NPC43508
0.5789 Remote Similarity NPC25817
0.5781 Remote Similarity NPC232673
0.5758 Remote Similarity NPC246947
0.5692 Remote Similarity NPC470236
0.5679 Remote Similarity NPC469654
0.5645 Remote Similarity NPC251102
0.5645 Remote Similarity NPC210298
0.5625 Remote Similarity NPC104167
0.561 Remote Similarity NPC223335
0.561 Remote Similarity NPC40920
0.5606 Remote Similarity NPC294166
0.5606 Remote Similarity NPC115022
0.5556 Remote Similarity NPC481303
0.5542 Remote Similarity NPC44507
0.5522 Remote Similarity NPC479030
0.5493 Remote Similarity NPC158635
0.5493 Remote Similarity NPC229882
0.5455 Remote Similarity NPC100389
0.5424 Remote Similarity NPC299144
0.5375 Remote Similarity NPC269559
0.5362 Remote Similarity NPC475084
0.5345 Remote Similarity NPC153149
0.5342 Remote Similarity NPC38041
0.5342 Remote Similarity NPC18979
0.5342 Remote Similarity NPC22150
0.5294 Remote Similarity NPC179309
0.527 Remote Similarity NPC471063
0.5263 Remote Similarity NPC276195
0.5263 Remote Similarity NPC212729
0.5263 Remote Similarity NPC604498
0.5246 Remote Similarity NPC69513
0.5205 Remote Similarity NPC286235
0.5172 Remote Similarity NPC217854
0.5172 Remote Similarity NPC269242
0.5167 Remote Similarity NPC60589
0.5167 Remote Similarity NPC469708
0.5167 Remote Similarity NPC609376
0.5161 Remote Similarity NPC48863
0.5161 Remote Similarity NPC251981
0.5161 Remote Similarity NPC13745
0.5143 Remote Similarity NPC98777
0.5135 Remote Similarity NPC227902
0.5135 Remote Similarity NPC279298
0.5128 Remote Similarity NPC157816
0.5128 Remote Similarity NPC470413
0.5085 Remote Similarity NPC294470
0.5082 Remote Similarity NPC226712
0.5082 Remote Similarity NPC608788
0.5079 Remote Similarity NPC215833
0.5077 Remote Similarity NPC26080
0.5077 Remote Similarity NPC165686
0.5072 Remote Similarity NPC186418
0.5072 Remote Similarity NPC202700
0.5072 Remote Similarity NPC185778

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC55040 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
0.5082 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