Natural Product: NPC104167

Natural Product IDNPC104167
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2R,3S,4S,5R,6S)-2-(Hydroxymethyl)-6-[3-[(E)-3-Hydroxyprop-1-Enyl]-2,5-Dimethoxyphenoxy]Oxane-3,4,5-Triol
IUPAC Name (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[3-[(E)-3-hydroxyprop-1-enyl]-2,5-dimethoxyphenoxy]oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479669
PubChem CID 10785494
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 SPPYYXOQQMWVFK-QNHGNZIUSA-N
Standard InCHI InChI=1S/C17H24O9/c1-23-10-6-9(4-3-5-18)16(24-2)11(7-10)25-17-15(22)14(21)13(20)12(8-19)26-17/h3-4,6-7,12-15,17-22H,5,8H2,1-2H3/b4-3+/t12-,13-,14+,15-,17-/m1/s1
SMILES OC/C=C/c1cc(OC)cc(c1OC)O[C@@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.14 Volume:   354.041
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Van der Waals volume.
Dense:   1.051 LogP:   0.187
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.809
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.456
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   13.0
TPSA:   138.07
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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:   0.403 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.838 Fsp3:   0.529
MCE-18:   50.769
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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:   0.385 Fluc inhibitor:   0.032
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.271
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.208
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.243 Promiscuous compounds:   0.332

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.494 MDCK Permeability:   -4.991
Pgp-inhibitor:   0.002 Pgp-substrate:   0.215
PAMPA:   0.779
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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):   0.807
20% Bioavailability (F20%):   0.206 30% Bioavailability (F30%):   0.922
50% Bioavailability (F50%):   0.831

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.051 MRP1:   0.027
Plasma Protein Binding (PPB):   64.722% Volume Distribution (VD):   -0.233
Fu: 33.68%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.199
BSEP inhibitor:   0.005

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:   0.013
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.062
HLM stability:   0.003
?
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):  2.464 Half-life (T1/2):  3.202

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.075
Human Hepatotoxicity (H-HT):  0.824 Drug-induced Liver Injury (DILI):  0.879
AMES Toxicity:  0.867 Rat Oral Acute Toxicity:  0.009
Maximum Recommended Daily Dose:  0.034 Skin Sensitization:  0.993
Carcinogencity:  0.3 Eye Corrosion:  0.0
Eye Irritation:  0.255 Respiratory Toxicity:  0.026
Drug-induced Neurotoxicity:  0.045 Ototoxicity:  0.923
Hematotoxicity:  0.421 Drug-induced Nephrotoxicity:  0.683
Genotoxicity:  0.393 RPMI-8226 Immunitoxicity:  0.14
A549 Cytotoxicity:  0.14 Hek293 Cytotoxicity:  0.188
BCF:   0.321
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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:   2.506
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.078
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.285
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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
NPO23424 Dirca palustris Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[10579873]
NPO23424 Dirca palustris Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[26225905]
NPO23424 Dirca palustris Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23424 Dirca palustris Species Thymelaeaceae 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
NPT324 Individual protein Cyclooxygenase-1 Ovis aries Inhibition = 9.2 % PMID[12105963]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC104167 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
0.6552 Remote Similarity NPC49074
0.65 Remote Similarity NPC248355
0.6111 Remote Similarity NPC276195
0.6071 Remote Similarity NPC25817
0.6 Remote Similarity NPC217854
0.5893 Remote Similarity NPC153149
0.5645 Remote Similarity NPC162093
0.5625 Remote Similarity NPC55040
0.5614 Remote Similarity NPC192810
0.5556 Remote Similarity NPC210478
0.5538 Remote Similarity NPC302378
0.55 Remote Similarity NPC145900
0.5441 Remote Similarity NPC164857
0.5424 Remote Similarity NPC299144
0.541 Remote Similarity NPC166040
0.5397 Remote Similarity NPC472024
0.5397 Remote Similarity NPC479028
0.5397 Remote Similarity NPC270849
0.5397 Remote Similarity NPC479031
0.537 Remote Similarity NPC228907
0.5333 Remote Similarity NPC200092
0.5303 Remote Similarity NPC232673
0.5294 Remote Similarity NPC479030
0.5294 Remote Similarity NPC37468
0.5246 Remote Similarity NPC69513
0.5231 Remote Similarity NPC479029
0.5224 Remote Similarity NPC470236
0.5195 Remote Similarity NPC43508
0.5161 Remote Similarity NPC48863
0.5161 Remote Similarity NPC251981
0.5161 Remote Similarity NPC13745
0.5156 Remote Similarity NPC604356
0.5079 Remote Similarity NPC215833
0.5079 Remote Similarity NPC9912
0.5077 Remote Similarity NPC26653
0.5077 Remote Similarity NPC214910
0.5077 Remote Similarity NPC80600
0.5075 Remote Similarity NPC247146
0.5065 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 NPC104167 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
NPD

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