Natural Product: NPC497455

Natural Product IDNPC497455
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Eucalmainoside B
IUPAC Name (2~{S},3~{R},4~{S},5~{S},6~{R})-2-(3,5-dihydroxy-2,4-dimethyl-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 NIPGLKKTAQBXAY-RGCYKPLRSA-N
Standard InCHI InChI=1S/C14H20O8/c1-5-7(16)3-8(6(2)10(5)17)21-14-13(20)12(19)11(18)9(4-15)22-14/h3,9,11-20H,4H2,1-2H3/t9-,11-,12+,13-,14-/m1/s1
SMILES CC1=C(O)C=C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C(C)=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.12 Volume:   296.0
?
Van der Waals volume.
Dense:   1.068 LogP:   0.226
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.803
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.706
?
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:   0.413 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.799 Fsp3:   0.571
MCE-18:   55.273
?
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:   0.484 Fluc inhibitor:   0.157
?
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:   0.031
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.253 Promiscuous compounds:   0.305

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.319 MDCK Permeability:   -5.176
Pgp-inhibitor:   0.0 Pgp-substrate:   0.103
PAMPA:   0.99
?
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):   0.349
20% Bioavailability (F20%):   0.235 30% Bioavailability (F30%):   0.906
50% Bioavailability (F50%):   0.879

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.147 MRP1:   0.727
Plasma Protein Binding (PPB):   75.973% Volume Distribution (VD):   -0.087
Fu: 24.851%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.015
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.903 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.163 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.016 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.014 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.01
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.602
HLM stability:   0.027
?
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):  3.038 Half-life (T1/2):  3.225

ADMET: Toxicity

hERG Blockers:  0.01 hERG Blockers (10um):  0.121
Human Hepatotoxicity (H-HT):  0.663 Drug-induced Liver Injury (DILI):  0.605
AMES Toxicity:  0.885 Rat Oral Acute Toxicity:  0.064
Maximum Recommended Daily Dose:  0.018 Skin Sensitization:  0.998
Carcinogencity:  0.238 Eye Corrosion:  0.002
Eye Irritation:  0.867 Respiratory Toxicity:  0.247
Drug-induced Neurotoxicity:  0.01 Ototoxicity:  0.889
Hematotoxicity:  0.312 Drug-induced Nephrotoxicity:  0.381
Genotoxicity:  0.379 RPMI-8226 Immunitoxicity:  0.107
A549 Cytotoxicity:  0.247 Hek293 Cytotoxicity:  0.229
BCF:   0.223
?
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:   2.442
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.14
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.973
?
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 NPC497455 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
0.7069 Intermediate Similarity NPC600107
0.6154 Remote Similarity NPC152722
0.5926 Remote Similarity NPC12308
0.5902 Remote Similarity NPC134260
0.5714 Remote Similarity NPC214454
0.5714 Remote Similarity NPC604209
0.569 Remote Similarity NPC23084
0.5667 Remote Similarity NPC222455
0.5667 Remote Similarity NPC106025
0.5636 Remote Similarity NPC226712
0.5636 Remote Similarity NPC608788
0.5625 Remote Similarity NPC210192
0.5614 Remote Similarity NPC40377
0.5577 Remote Similarity NPC212729
0.5577 Remote Similarity NPC142319
0.5577 Remote Similarity NPC604498
0.5556 Remote Similarity NPC610808
0.5484 Remote Similarity NPC199335
0.5484 Remote Similarity NPC477240
0.5472 Remote Similarity NPC217854
0.5472 Remote Similarity NPC269242
0.5472 Remote Similarity NPC484157
0.5469 Remote Similarity NPC604892
0.5455 Remote Similarity NPC278329
0.5455 Remote Similarity NPC299144
0.5455 Remote Similarity NPC271385
0.5455 Remote Similarity NPC146837
0.5455 Remote Similarity NPC30432
0.5439 Remote Similarity NPC166168
0.541 Remote Similarity NPC599943
0.54 Remote Similarity NPC228907
0.5397 Remote Similarity NPC190217
0.537 Remote Similarity NPC192810
0.537 Remote Similarity NPC294470
0.5312 Remote Similarity NPC111536
0.5303 Remote Similarity NPC99233
0.5283 Remote Similarity NPC276195
0.5273 Remote Similarity NPC9248
0.5263 Remote Similarity NPC69513
0.5263 Remote Similarity NPC145900
0.5254 Remote Similarity NPC218685
0.5246 Remote Similarity NPC609351
0.5238 Remote Similarity NPC475628
0.5224 Remote Similarity NPC5029
0.5224 Remote Similarity NPC605700
0.5224 Remote Similarity NPC606849
0.5211 Remote Similarity NPC472320
0.5179 Remote Similarity NPC60589
0.5179 Remote Similarity NPC469708
0.5179 Remote Similarity NPC609376
0.5172 Remote Similarity NPC48863
0.5172 Remote Similarity NPC251981
0.5172 Remote Similarity NPC13745
0.5167 Remote Similarity NPC485268
0.5167 Remote Similarity NPC205054
0.5167 Remote Similarity NPC19470
0.5167 Remote Similarity NPC606892
0.5156 Remote Similarity NPC611586
0.5152 Remote Similarity NPC302989
0.5147 Remote Similarity NPC101116
0.5088 Remote Similarity NPC200092
0.5085 Remote Similarity NPC310661
0.5085 Remote Similarity NPC215833
0.5082 Remote Similarity NPC214910
0.5082 Remote Similarity NPC26080
0.5082 Remote Similarity NPC210015
0.5082 Remote Similarity NPC165686
0.5082 Remote Similarity NPC481303
0.5079 Remote Similarity NPC85799
0.5079 Remote Similarity NPC303422
0.5079 Remote Similarity NPC218003
0.5079 Remote Similarity NPC97326
0.5079 Remote Similarity NPC607971
0.5079 Remote Similarity NPC609355
0.5077 Remote Similarity NPC8497
0.5077 Remote Similarity NPC479374
0.5075 Remote Similarity NPC177742
0.5072 Remote Similarity NPC212099
0.5072 Remote Similarity NPC259182
0.5072 Remote Similarity NPC88484
0.5072 Remote Similarity NPC76128
0.5072 Remote Similarity NPC606202

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC497455 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
0.5636 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