Natural Product: NPC533452

Natural Product IDNPC533452
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Eucalmainoside A
IUPAC Name (2~{S},3~{R},4~{S},5~{S},6~{R})-2-(3,5-dihydroxy-2-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 AXTQBXDFUAAFPD-UJPOAAIJSA-N
Standard InCHI InChI=1S/C13H18O8/c1-5-7(16)2-6(15)3-8(5)20-13-12(19)11(18)10(17)9(4-14)21-13/h2-3,9-19H,4H2,1H3/t9-,10-,11+,12-,13-/m1/s1
SMILES CC1=C(O)C=C(O)C=C1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.1 Volume:   278.704
?
Van der Waals volume.
Dense:   1.084 LogP:   -0.227
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.326
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.401
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 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:   0.4 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.731 Fsp3:   0.538
MCE-18:   52.5
?
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:   0.535 Fluc inhibitor:   0.076
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.153
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.031
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.236 Promiscuous compounds:   0.304

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.395 MDCK Permeability:   -5.109
Pgp-inhibitor:   0.0 Pgp-substrate:   0.265
PAMPA:   0.935
?
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):   0.07
20% Bioavailability (F20%):   0.218 30% Bioavailability (F30%):   0.95
50% Bioavailability (F50%):   0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.282 MRP1:   0.578
Plasma Protein Binding (PPB):   61.291% Volume Distribution (VD):   -0.334
Fu: 36.287%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.088
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.319 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.018 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.014 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.462
HLM stability:   0.102
?
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):  2.837 Half-life (T1/2):  3.736

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.151
Human Hepatotoxicity (H-HT):  0.612 Drug-induced Liver Injury (DILI):  0.582
AMES Toxicity:  0.891 Rat Oral Acute Toxicity:  0.04
Maximum Recommended Daily Dose:  0.044 Skin Sensitization:  0.996
Carcinogencity:  0.305 Eye Corrosion:  0.003
Eye Irritation:  0.886 Respiratory Toxicity:  0.066
Drug-induced Neurotoxicity:  0.012 Ototoxicity:  0.838
Hematotoxicity:  0.182 Drug-induced Nephrotoxicity:  0.364
Genotoxicity:  0.592 RPMI-8226 Immunitoxicity:  0.082
A549 Cytotoxicity:  0.276 Hek293 Cytotoxicity:  0.331
BCF:   0.283
?
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:   1.939
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.287
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.525
?
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
NPO9838 Eucalyptus maideni Species Myrtaceae Eukaryota fresh leaves n.a. n.a. PMID[19778089]
NPO9838 Eucalyptus maideni Species Myrtaceae Eukaryota fresh fruits n.a. n.a. PMID[20092288]
NPO9838 Eucalyptus maideni Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9838 Eucalyptus maideni Species Myrtaceae 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 NPC533452 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
0.7091 Intermediate Similarity NPC106025
0.6842 Remote Similarity NPC199335
0.6842 Remote Similarity NPC477240
0.6724 Remote Similarity NPC190217
0.6471 Remote Similarity NPC152722
0.6226 Remote Similarity NPC12308
0.6078 Remote Similarity NPC484157
0.6 Remote Similarity NPC259182
0.6 Remote Similarity NPC88484
0.5902 Remote Similarity NPC134260
0.5893 Remote Similarity NPC40377
0.5882 Remote Similarity NPC142319
0.5821 Remote Similarity NPC257963
0.5714 Remote Similarity NPC214454
0.5692 Remote Similarity NPC271385
0.5692 Remote Similarity NPC5029
0.569 Remote Similarity NPC23084
0.5672 Remote Similarity NPC26195
0.5625 Remote Similarity NPC210192
0.5484 Remote Similarity NPC475628
0.5472 Remote Similarity NPC217854
0.5469 Remote Similarity NPC600107
0.5469 Remote Similarity NPC604892
0.5455 Remote Similarity NPC299144
0.5439 Remote Similarity NPC604209
0.541 Remote Similarity NPC599943
0.54 Remote Similarity NPC228907
0.537 Remote Similarity NPC192810
0.5357 Remote Similarity NPC226712
0.5357 Remote Similarity NPC608788
0.5333 Remote Similarity NPC26080
0.5333 Remote Similarity NPC165686
0.5323 Remote Similarity NPC97326
0.5303 Remote Similarity NPC99233
0.5283 Remote Similarity NPC276195
0.5283 Remote Similarity NPC212729
0.5283 Remote Similarity NPC604498
0.5273 Remote Similarity NPC9248
0.5263 Remote Similarity NPC69513
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 NPC30432
0.5224 Remote Similarity NPC601828
0.5224 Remote Similarity NPC606849
0.5185 Remote Similarity NPC269242
0.5179 Remote Similarity NPC60589
0.5179 Remote Similarity NPC469708
0.5172 Remote Similarity NPC48863
0.5172 Remote Similarity NPC166168
0.5172 Remote Similarity NPC251981
0.5172 Remote Similarity NPC13745
0.5167 Remote Similarity NPC19470
0.5167 Remote Similarity NPC606892
0.5161 Remote Similarity NPC222455
0.5156 Remote Similarity NPC611586
0.5152 Remote Similarity NPC302989
0.5147 Remote Similarity NPC169248
0.5147 Remote Similarity NPC72649
0.5091 Remote Similarity NPC294470
0.5085 Remote Similarity NPC310661
0.5085 Remote Similarity NPC215833
0.5085 Remote Similarity NPC9912
0.5082 Remote Similarity NPC214910
0.5082 Remote Similarity NPC210015
0.5079 Remote Similarity NPC59324
0.5079 Remote Similarity NPC85799
0.5079 Remote Similarity NPC303422
0.5079 Remote Similarity NPC218003
0.5077 Remote Similarity NPC111536
0.5077 Remote Similarity NPC8497
0.5077 Remote Similarity NPC610808
0.5075 Remote Similarity NPC259767
0.5075 Remote Similarity NPC177742
0.5072 Remote Similarity NPC479692

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC533452 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
0.5357 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