Natural Product: NPC59705

Natural Product IDNPC59705
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AYMJCHHSHFRKRI-TVKJYDDYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11256426
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 AYMJCHHSHFRKRI-TVKJYDDYSA-N
Standard InCHI InChI=1S/C15H20O9/c1-22-11(18)5-7-4-8(17)2-3-9(7)23-15-14(21)13(20)12(19)10(6-16)24-15/h2-4,10,12-17,19-21H,5-6H2,1H3/t10-,12-,13+,14-,15-/m1/s1
SMILES COC(=O)Cc1cc(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:   344.11 Volume:   319.45
?
Van der Waals volume.
Dense:   1.077 LogP:   -0.681
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.072
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.311
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
TPSA:   145.91
?
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:   0.394 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.597 Fsp3:   0.533
MCE-18:   51.522
?
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:   0.498 Fluc inhibitor:   0.048
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.116
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.155
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.127 Promiscuous compounds:   0.405

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.095 MDCK Permeability:   -5.011
Pgp-inhibitor:   0.0 Pgp-substrate:   0.002
PAMPA:   0.981
?
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):   0.029
20% Bioavailability (F20%):   0.176 30% Bioavailability (F30%):   0.81
50% Bioavailability (F50%):   0.832

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.154
Plasma Protein Binding (PPB):   51.263% Volume Distribution (VD):   -0.46
Fu: 45.86%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.001
BSEP inhibitor:   0.004

ADMET: Metabolism

CYP1A2-inhibitor:   0.089 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.159 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.005 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.051
HLM stability:   0.182
?
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):  3.612 Half-life (T1/2):  2.617

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.148
Human Hepatotoxicity (H-HT):  0.514 Drug-induced Liver Injury (DILI):  0.647
AMES Toxicity:  0.832 Rat Oral Acute Toxicity:  0.058
Maximum Recommended Daily Dose:  0.016 Skin Sensitization:  0.998
Carcinogencity:  0.213 Eye Corrosion:  0.0
Eye Irritation:  0.37 Respiratory Toxicity:  0.029
Drug-induced Neurotoxicity:  0.03 Ototoxicity:  0.862
Hematotoxicity:  0.265 Drug-induced Nephrotoxicity:  0.637
Genotoxicity:  0.368 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.034 Hek293 Cytotoxicity:  0.104
BCF:   0.241
?
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:   2.23
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.68
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.966
?
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
NPO13524 Pyrola japonica Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13524 Pyrola japonica Species Ericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13524 Pyrola japonica Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13524 Pyrola japonica Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13524 Pyrola japonica Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13524 Pyrola japonica Species Ericaceae 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 NPC59705 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
0.7288 Intermediate Similarity NPC97326
0.6842 Remote Similarity NPC40377
0.6 Remote Similarity NPC142319
0.5714 Remote Similarity NPC299435
0.5692 Remote Similarity NPC34456
0.569 Remote Similarity NPC152722
0.5571 Remote Similarity NPC92054
0.5556 Remote Similarity NPC260604
0.5429 Remote Similarity NPC177742
0.541 Remote Similarity NPC69513
0.5405 Remote Similarity NPC145319
0.5395 Remote Similarity NPC474422
0.5373 Remote Similarity NPC475628
0.5352 Remote Similarity NPC148273
0.5345 Remote Similarity NPC484157
0.5333 Remote Similarity NPC60589
0.5333 Remote Similarity NPC469708
0.5312 Remote Similarity NPC19470
0.5286 Remote Similarity NPC210192
0.527 Remote Similarity NPC106625
0.5246 Remote Similarity NPC12308
0.5246 Remote Similarity NPC608788
0.5238 Remote Similarity NPC310661
0.5238 Remote Similarity NPC215833
0.5231 Remote Similarity NPC210015
0.5217 Remote Similarity NPC185778
0.5205 Remote Similarity NPC259182
0.5167 Remote Similarity NPC9248
0.5161 Remote Similarity NPC221090
0.5147 Remote Similarity NPC100389
0.5147 Remote Similarity NPC269421
0.5143 Remote Similarity NPC121001
0.5139 Remote Similarity NPC601828
0.5135 Remote Similarity NPC61594
0.5085 Remote Similarity NPC217854
0.5082 Remote Similarity NPC299144
0.5079 Remote Similarity NPC48863
0.5079 Remote Similarity NPC251981
0.5079 Remote Similarity NPC13745
0.5077 Remote Similarity NPC472024
0.5077 Remote Similarity NPC270849
0.5077 Remote Similarity NPC23084
0.5075 Remote Similarity NPC106025
0.5072 Remote Similarity NPC134260
0.5072 Remote Similarity NPC469661
0.5072 Remote Similarity NPC611586
0.507 Remote Similarity NPC189115
0.507 Remote Similarity NPC475096
0.5067 Remote Similarity NPC56735
0.5067 Remote Similarity NPC147596
0.5067 Remote Similarity NPC257963

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59705 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