Natural Product: NPC523434

Natural Product IDNPC523434
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Zataroside A
IUPAC Name (2~{S},3~{R},4~{S},5~{S},6~{R})-2-(4-hydroxy-2-isopropyl-5-methyl-phenoxy)-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 KSNLTHGWURXRJK-IBEHDNSVSA-N
Standard InCHI InChI=1S/C16H24O7/c1-7(2)9-5-10(18)8(3)4-11(9)22-16-15(21)14(20)13(19)12(6-17)23-16/h4-5,7,12-21H,6H2,1-3H3/t12-,13-,14+,15-,16-/m1/s1
SMILES CC1=CC(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)=C(C(C)C)C=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.15 Volume:   321.802
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Van der Waals volume.
Dense:   1.02 LogP:   1.051
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.671
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.103
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   119.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.528 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.696 Fsp3:   0.625
MCE-18:   54.154
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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:   0.627 Fluc inhibitor:   0.021
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.117
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.072
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.254 Promiscuous compounds:   0.074

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.585 MDCK Permeability:   -5.121
Pgp-inhibitor:   0.002 Pgp-substrate:   0.03
PAMPA:   0.408
?
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):   0.024
20% Bioavailability (F20%):   0.14 30% Bioavailability (F30%):   0.922
50% Bioavailability (F50%):   0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.02 MRP1:   0.955
Plasma Protein Binding (PPB):   80.247% Volume Distribution (VD):   0.044
Fu: 21.654%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.014
BSEP inhibitor:   0.501

ADMET: Metabolism

CYP1A2-inhibitor:   0.681 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.015 CYP2C19-substrate:   0.011
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.025
CYP3A4-inhibitor:   0.023 CYP3A4-substrate:   0.068
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.944
HLM stability:   0.135
?
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):  3.266 Half-life (T1/2):  2.896

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.16
Human Hepatotoxicity (H-HT):  0.718 Drug-induced Liver Injury (DILI):  0.637
AMES Toxicity:  0.811 Rat Oral Acute Toxicity:  0.039
Maximum Recommended Daily Dose:  0.029 Skin Sensitization:  0.992
Carcinogencity:  0.355 Eye Corrosion:  0.001
Eye Irritation:  0.536 Respiratory Toxicity:  0.043
Drug-induced Neurotoxicity:  0.023 Ototoxicity:  0.939
Hematotoxicity:  0.446 Drug-induced Nephrotoxicity:  0.735
Genotoxicity:  0.142 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.158 Hek293 Cytotoxicity:  0.174
BCF:   0.648
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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:   3.16
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.555
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.805
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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
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23189738]
NPO52176 Origanum syriacum Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37049808]
NPO52176 Origanum syriacum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO48088 Origanum svriacum Genus Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1059 Sphaeranthus bullatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1059 Sphaeranthus bullatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8881 Centipeda minima Species Asteraceae 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 NPC523434 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
0.6111 Remote Similarity NPC12308
0.6066 Remote Similarity NPC134260
0.5833 Remote Similarity NPC599943
0.5789 Remote Similarity NPC40377
0.5741 Remote Similarity NPC152722
0.5636 Remote Similarity NPC299144
0.5614 Remote Similarity NPC214454
0.5614 Remote Similarity NPC604209
0.5606 Remote Similarity NPC5029
0.5593 Remote Similarity NPC23084
0.5574 Remote Similarity NPC106025
0.5538 Remote Similarity NPC210192
0.5536 Remote Similarity NPC608788
0.5484 Remote Similarity NPC97326
0.5472 Remote Similarity NPC142319
0.5469 Remote Similarity NPC111536
0.5469 Remote Similarity NPC610808
0.5441 Remote Similarity NPC76128
0.5439 Remote Similarity NPC69513
0.5397 Remote Similarity NPC199335
0.5397 Remote Similarity NPC475628
0.5397 Remote Similarity NPC477240
0.5385 Remote Similarity NPC600107
0.5385 Remote Similarity NPC604892
0.5373 Remote Similarity NPC278329
0.5373 Remote Similarity NPC271385
0.5373 Remote Similarity NPC146837
0.5373 Remote Similarity NPC30432
0.537 Remote Similarity NPC217854
0.537 Remote Similarity NPC484157
0.5345 Remote Similarity NPC48863
0.5345 Remote Similarity NPC251981
0.5345 Remote Similarity NPC13745
0.5333 Remote Similarity NPC205054
0.5323 Remote Similarity NPC222455
0.5312 Remote Similarity NPC190217
0.5312 Remote Similarity NPC611586
0.5294 Remote Similarity NPC101116
0.5294 Remote Similarity NPC228907
0.5273 Remote Similarity NPC192810
0.5273 Remote Similarity NPC294470
0.5263 Remote Similarity NPC226712
0.5254 Remote Similarity NPC310661
0.5254 Remote Similarity NPC215833
0.5246 Remote Similarity NPC210015
0.5246 Remote Similarity NPC481303
0.5238 Remote Similarity NPC218003
0.5217 Remote Similarity NPC212099
0.5185 Remote Similarity NPC276195
0.5185 Remote Similarity NPC212729
0.5185 Remote Similarity NPC604498
0.5179 Remote Similarity NPC9248
0.5167 Remote Similarity NPC218685
0.5167 Remote Similarity NPC49074
0.5161 Remote Similarity NPC105827
0.5147 Remote Similarity NPC605700
0.5147 Remote Similarity NPC606849
0.5091 Remote Similarity NPC269242
0.5088 Remote Similarity NPC60589
0.5088 Remote Similarity NPC469708
0.5085 Remote Similarity NPC166168
0.5082 Remote Similarity NPC162093
0.5082 Remote Similarity NPC19470
0.5082 Remote Similarity NPC606892
0.5079 Remote Similarity NPC95392
0.5079 Remote Similarity NPC84013
0.5079 Remote Similarity NPC55715
0.5079 Remote Similarity NPC35877
0.5075 Remote Similarity NPC302989
0.5072 Remote Similarity NPC212290
0.5072 Remote Similarity NPC604833

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC523434 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
0.5263 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