Natural Product: NPC57224

Natural Product IDNPC57224
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AWHHJEGHYHOVRN-UJPOAAIJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11972338
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 AWHHJEGHYHOVRN-UJPOAAIJSA-N
Standard InCHI InChI=1S/C13H18O8/c14-4-6-1-2-8(7(16)3-6)20-13-12(19)11(18)10(17)9(5-15)21-13/h1-3,9-19H,4-5H2/t9-,10-,11+,12-,13-/m1/s1
SMILES c1cc(c(cc1CO)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.1 Volume:   278.704
?
Van der Waals volume.
Dense:   1.084 LogP:   -0.942
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.334
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.988
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   139.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   6.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.378 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.552 Fsp3:   0.538
MCE-18:   49.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.429 Fluc inhibitor:   0.061
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.083
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.038
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.38 Promiscuous compounds:   0.231

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.473 MDCK Permeability:   -5.001
Pgp-inhibitor:   0.0 Pgp-substrate:   0.038
PAMPA:   0.983
?
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):   0.902
20% Bioavailability (F20%):   0.496 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   0.923

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.144 MRP1:   0.051
Plasma Protein Binding (PPB):   58.593% Volume Distribution (VD):   -0.348
Fu: 42.371%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.022
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.018 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.589
HLM stability:   0.013
?
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):  2.809 Half-life (T1/2):  3.238

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.092
Human Hepatotoxicity (H-HT):  0.607 Drug-induced Liver Injury (DILI):  0.552
AMES Toxicity:  0.819 Rat Oral Acute Toxicity:  0.011
Maximum Recommended Daily Dose:  0.011 Skin Sensitization:  0.984
Carcinogencity:  0.285 Eye Corrosion:  0.001
Eye Irritation:  0.654 Respiratory Toxicity:  0.025
Drug-induced Neurotoxicity:  0.025 Ototoxicity:  0.898
Hematotoxicity:  0.215 Drug-induced Nephrotoxicity:  0.588
Genotoxicity:  0.554 RPMI-8226 Immunitoxicity:  0.077
A549 Cytotoxicity:  0.077 Hek293 Cytotoxicity:  0.098
BCF:   0.251
?
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:   1.955
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.477
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.649
?
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
NPO12682 Euphorbia helioscopia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[18321057]
NPO12682 Euphorbia helioscopia Species Euphorbiaceae Eukaryota n.a. whole plant n.a. PMID[19099222]
NPO12682 Euphorbia helioscopia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[30724086]
NPO12682 Euphorbia helioscopia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[31550154]
NPO12682 Euphorbia helioscopia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28586 Pyrus calleryana Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12682 Euphorbia helioscopia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12682 Euphorbia helioscopia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28586 Pyrus calleryana Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12682 Euphorbia helioscopia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28586 Pyrus calleryana Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12682 Euphorbia helioscopia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28586 Pyrus calleryana Species Rosaceae 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

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 NPC57224 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
0.717 Intermediate Similarity NPC19470
0.7083 Intermediate Similarity NPC269242
0.7037 Intermediate Similarity NPC481303
0.68 Remote Similarity NPC9248
0.6667 Remote Similarity NPC59324
0.6552 Remote Similarity NPC100389
0.6333 Remote Similarity NPC186418
0.6333 Remote Similarity NPC202700
0.6296 Remote Similarity NPC166168
0.6296 Remote Similarity NPC166040
0.625 Remote Similarity NPC205054
0.6182 Remote Similarity NPC40377
0.614 Remote Similarity NPC210015
0.6129 Remote Similarity NPC106944
0.5938 Remote Similarity NPC116229
0.5926 Remote Similarity NPC226712
0.5893 Remote Similarity NPC310661
0.5882 Remote Similarity NPC212729
0.5882 Remote Similarity NPC142319
0.5882 Remote Similarity NPC604498
0.5818 Remote Similarity NPC221090
0.5769 Remote Similarity NPC484157
0.5763 Remote Similarity NPC105827
0.5758 Remote Similarity NPC191046
0.5741 Remote Similarity NPC299144
0.5741 Remote Similarity NPC60589
0.5741 Remote Similarity NPC469708
0.5714 Remote Similarity NPC228907
0.5667 Remote Similarity NPC25292
0.566 Remote Similarity NPC192810
0.566 Remote Similarity NPC294470
0.5645 Remote Similarity NPC469661
0.5645 Remote Similarity NPC65530
0.5636 Remote Similarity NPC12308
0.5625 Remote Similarity NPC98777
0.5625 Remote Similarity NPC189115
0.5593 Remote Similarity NPC26080
0.5593 Remote Similarity NPC165686
0.5556 Remote Similarity NPC610808
0.5507 Remote Similarity NPC232228
0.5455 Remote Similarity NPC609376
0.5439 Remote Similarity NPC214454
0.5397 Remote Similarity NPC174377
0.5373 Remote Similarity NPC101116
0.5362 Remote Similarity NPC310064
0.5357 Remote Similarity NPC200092
0.5357 Remote Similarity NPC608788
0.5345 Remote Similarity NPC9912
0.5294 Remote Similarity NPC606202
0.5273 Remote Similarity NPC152722
0.5263 Remote Similarity NPC80098
0.5263 Remote Similarity NPC145900
0.5238 Remote Similarity NPC478871
0.5238 Remote Similarity NPC478870
0.5238 Remote Similarity NPC478872
0.5238 Remote Similarity NPC478873
0.5224 Remote Similarity NPC605700
0.5217 Remote Similarity NPC72249
0.5217 Remote Similarity NPC488085
0.5167 Remote Similarity NPC472024
0.5167 Remote Similarity NPC270849
0.5167 Remote Similarity NPC23084
0.5167 Remote Similarity NPC604356
0.5161 Remote Similarity NPC222455
0.5161 Remote Similarity NPC599943
0.5156 Remote Similarity NPC294166
0.5156 Remote Similarity NPC252169
0.5156 Remote Similarity NPC115022
0.5152 Remote Similarity NPC212770
0.5147 Remote Similarity NPC88043
0.5143 Remote Similarity NPC279298
0.5091 Remote Similarity NPC153149
0.5082 Remote Similarity NPC214910
0.5079 Remote Similarity NPC85799
0.5079 Remote Similarity NPC473045
0.5079 Remote Similarity NPC303422
0.5079 Remote Similarity NPC218003
0.5079 Remote Similarity NPC97326
0.5077 Remote Similarity NPC8497
0.5077 Remote Similarity NPC185778
0.5077 Remote Similarity NPC604095
0.5072 Remote Similarity NPC45400
0.5072 Remote Similarity NPC212099

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC57224 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
0.5926 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