Natural Product: NPC239275

Natural Product IDNPC239275
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GXBCTYRBTGLIQW-RKQHYHRCSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 127685
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 GXBCTYRBTGLIQW-RKQHYHRCSA-N
Standard InCHI InChI=1S/C14H18O8/c1-6(16)8-4-7(17)2-3-9(8)21-14-13(20)12(19)11(18)10(5-15)22-14/h2-4,10-15,17-20H,5H2,1H3/t10-,11-,12+,13-,14-/m1/s1
SMILES CC(=O)c1cc(ccc1O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.1 Volume:   293.363
?
Van der Waals volume.
Dense:   1.071 LogP:   -0.579
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.092
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.001
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   136.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.436 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.547 Fsp3:   0.5
MCE-18:   52.143
?
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:   0.478 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.216
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.051
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.273 Promiscuous compounds:   0.388

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.138 MDCK Permeability:   -4.982
Pgp-inhibitor:   0.0 Pgp-substrate:   0.209
PAMPA:   0.997
?
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):   0.225
20% Bioavailability (F20%):   0.05 30% Bioavailability (F30%):   0.743
50% Bioavailability (F50%):   0.891

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.111 MRP1:   0.57
Plasma Protein Binding (PPB):   48.661% Volume Distribution (VD):   -0.406
Fu: 47.877%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.004
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 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:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.09
HLM stability:   0.011
?
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):  3.607 Half-life (T1/2):  3.13

ADMET: Toxicity

hERG Blockers:  0.028 hERG Blockers (10um):  0.122
Human Hepatotoxicity (H-HT):  0.688 Drug-induced Liver Injury (DILI):  0.621
AMES Toxicity:  0.877 Rat Oral Acute Toxicity:  0.02
Maximum Recommended Daily Dose:  0.025 Skin Sensitization:  0.991
Carcinogencity:  0.324 Eye Corrosion:  0.0
Eye Irritation:  0.64 Respiratory Toxicity:  0.021
Drug-induced Neurotoxicity:  0.027 Ototoxicity:  0.879
Hematotoxicity:  0.375 Drug-induced Nephrotoxicity:  0.482
Genotoxicity:  0.53 RPMI-8226 Immunitoxicity:  0.084
A549 Cytotoxicity:  0.122 Hek293 Cytotoxicity:  0.203
BCF:   0.246
?
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:   2.439
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.906
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.176
?
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
NPO1254 Cynanchum bungei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1254 Cynanchum bungei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1254 Cynanchum bungei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1254 Cynanchum bungei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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 NPC239275 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
0.75 Intermediate Similarity NPC40377
0.7321 Intermediate Similarity NPC97326
0.66 Remote Similarity NPC142319
0.614 Remote Similarity NPC218685
0.6094 Remote Similarity NPC177742
0.6038 Remote Similarity NPC294470
0.6034 Remote Similarity NPC205054
0.6034 Remote Similarity NPC23084
0.6 Remote Similarity NPC92054
0.6 Remote Similarity NPC106025
0.5968 Remote Similarity NPC611586
0.5926 Remote Similarity NPC152722
0.5909 Remote Similarity NPC299435
0.5806 Remote Similarity NPC199335
0.5806 Remote Similarity NPC475628
0.5806 Remote Similarity NPC477240
0.5789 Remote Similarity NPC214454
0.5735 Remote Similarity NPC260604
0.5714 Remote Similarity NPC190217
0.5714 Remote Similarity NPC12308
0.5636 Remote Similarity NPC9248
0.5571 Remote Similarity NPC145319
0.5556 Remote Similarity NPC484157
0.5536 Remote Similarity NPC60589
0.5536 Remote Similarity NPC469708
0.5507 Remote Similarity NPC61594
0.55 Remote Similarity NPC19470
0.549 Remote Similarity NPC228907
0.5439 Remote Similarity NPC226712
0.5439 Remote Similarity NPC608788
0.5429 Remote Similarity NPC56735
0.5429 Remote Similarity NPC147596
0.5424 Remote Similarity NPC310661
0.541 Remote Similarity NPC26080
0.541 Remote Similarity NPC210015
0.541 Remote Similarity NPC165686
0.541 Remote Similarity NPC481303
0.5373 Remote Similarity NPC99233
0.537 Remote Similarity NPC212729
0.537 Remote Similarity NPC604498
0.5345 Remote Similarity NPC221090
0.5342 Remote Similarity NPC474422
0.5323 Remote Similarity NPC105827
0.5294 Remote Similarity NPC271385
0.5294 Remote Similarity NPC5029
0.5294 Remote Similarity NPC601828
0.5273 Remote Similarity NPC217854
0.5273 Remote Similarity NPC269242
0.5263 Remote Similarity NPC299144
0.5254 Remote Similarity NPC166168
0.5238 Remote Similarity NPC599943
0.5217 Remote Similarity NPC169248
0.5217 Remote Similarity NPC271479
0.5217 Remote Similarity NPC72649
0.5211 Remote Similarity NPC257963
0.5205 Remote Similarity NPC476203
0.5179 Remote Similarity NPC192810
0.5172 Remote Similarity NPC200092
0.5167 Remote Similarity NPC9912
0.5161 Remote Similarity NPC214910
0.5156 Remote Similarity NPC59324
0.5156 Remote Similarity NPC85799
0.5156 Remote Similarity NPC303422
0.5152 Remote Similarity NPC610808
0.5143 Remote Similarity NPC308265
0.5143 Remote Similarity NPC259182
0.5143 Remote Similarity NPC88484
0.5143 Remote Similarity NPC170475
0.5139 Remote Similarity NPC607365
0.5135 Remote Similarity NPC23817
0.5091 Remote Similarity NPC276195
0.5085 Remote Similarity NPC69513
0.5079 Remote Similarity NPC57751
0.5077 Remote Similarity NPC478871
0.5077 Remote Similarity NPC478870
0.5077 Remote Similarity NPC478872
0.5077 Remote Similarity NPC478873
0.5075 Remote Similarity NPC474044
0.5075 Remote Similarity NPC216752
0.5075 Remote Similarity NPC121001
0.5072 Remote Similarity NPC278329
0.5072 Remote Similarity NPC148273
0.5072 Remote Similarity NPC146837
0.507 Remote Similarity NPC471457
0.5067 Remote Similarity NPC259834

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC239275 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
0.5439 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