Natural Product: NPC518554

Natural Product IDNPC518554
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 20274-94-6
IUPAC Name (2~{R},3~{S},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-(4-methylphenoxy)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 MVLBSNPILSLTFZ-UJPOAAIJSA-N
Standard InCHI InChI=1S/C13H18O6/c1-7-2-4-8(5-3-7)18-13-12(17)11(16)10(15)9(6-14)19-13/h2-5,9-17H,6H2,1H3/t9-,10-,11+,12-,13-/m1/s1
SMILES CC1=CC=C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   270.11 Volume:   261.123
?
Van der Waals volume.
Dense:   1.034 LogP:   0.511
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.935
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.543
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   12.0
TPSA:   99.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.572 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.217 Fsp3:   0.538
MCE-18:   45.5
?
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:   0.484 Fluc inhibitor:   0.007
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.068
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.04
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.316 Promiscuous compounds:   0.034

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.688 MDCK Permeability:   -4.946
Pgp-inhibitor:   0.005 Pgp-substrate:   0.152
PAMPA:   0.952
?
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):   0.177
20% Bioavailability (F20%):   0.045 30% Bioavailability (F30%):   0.513
50% Bioavailability (F50%):   0.549

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.824 MRP1:   0.165
Plasma Protein Binding (PPB):   74.536% Volume Distribution (VD):   -0.353
Fu: 25.343%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.006
BSEP inhibitor:   0.121

ADMET: Metabolism

CYP1A2-inhibitor:   0.033 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.036 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.033 CYP3A4-substrate:   0.006
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.379
HLM stability:   0.03
?
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):  3.141 Half-life (T1/2):  3.051

ADMET: Toxicity

hERG Blockers:  0.045 hERG Blockers (10um):  0.174
Human Hepatotoxicity (H-HT):  0.638 Drug-induced Liver Injury (DILI):  0.725
AMES Toxicity:  0.851 Rat Oral Acute Toxicity:  0.03
Maximum Recommended Daily Dose:  0.016 Skin Sensitization:  0.992
Carcinogencity:  0.332 Eye Corrosion:  0.004
Eye Irritation:  0.684 Respiratory Toxicity:  0.024
Drug-induced Neurotoxicity:  0.057 Ototoxicity:  0.866
Hematotoxicity:  0.41 Drug-induced Nephrotoxicity:  0.636
Genotoxicity:  0.087 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.128 Hek293 Cytotoxicity:  0.097
BCF:   0.625
?
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:   2.839
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.992
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.347
?
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
NPO62840 Gymnadenia conopsea R.BR. Genus Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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 NPC518554 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
0.8049 Intermediate Similarity NPC212729
0.8049 Intermediate Similarity NPC604498
0.7857 Intermediate Similarity NPC269242
0.7674 Intermediate Similarity NPC294470
0.7333 Intermediate Similarity NPC60589
0.7333 Intermediate Similarity NPC469708
0.7333 Intermediate Similarity NPC609376
0.7174 Intermediate Similarity NPC200092
0.7021 Intermediate Similarity NPC80098
0.6818 Remote Similarity NPC142319
0.68 Remote Similarity NPC251102
0.68 Remote Similarity NPC210298
0.6667 Remote Similarity NPC228907
0.6471 Remote Similarity NPC604356
0.6458 Remote Similarity NPC12308
0.6346 Remote Similarity NPC26080
0.6346 Remote Similarity NPC165686
0.6275 Remote Similarity NPC218685
0.625 Remote Similarity NPC604439
0.617 Remote Similarity NPC153149
0.6154 Remote Similarity NPC479028
0.6154 Remote Similarity NPC479031
0.6122 Remote Similarity NPC226712
0.6122 Remote Similarity NPC608788
0.6087 Remote Similarity NPC276195
0.6042 Remote Similarity NPC25817
0.5957 Remote Similarity NPC217854
0.5882 Remote Similarity NPC214454
0.5882 Remote Similarity NPC166040
0.5849 Remote Similarity NPC485268
0.5849 Remote Similarity NPC606892
0.5833 Remote Similarity NPC192810
0.5769 Remote Similarity NPC310661
0.5769 Remote Similarity NPC9912
0.5741 Remote Similarity NPC164599
0.5714 Remote Similarity NPC9248
0.5686 Remote Similarity NPC221090
0.5667 Remote Similarity NPC259767
0.5625 Remote Similarity NPC484157
0.5614 Remote Similarity NPC146540
0.56 Remote Similarity NPC299144
0.5577 Remote Similarity NPC166168
0.5574 Remote Similarity NPC471029
0.5556 Remote Similarity NPC472024
0.5556 Remote Similarity NPC270849
0.5556 Remote Similarity NPC83975
0.5556 Remote Similarity NPC205054
0.5556 Remote Similarity NPC23084
0.5556 Remote Similarity NPC19470
0.5536 Remote Similarity NPC222455
0.5517 Remote Similarity NPC294166
0.5517 Remote Similarity NPC115022
0.55 Remote Similarity NPC248119
0.55 Remote Similarity NPC210192
0.55 Remote Similarity NPC175275
0.5472 Remote Similarity NPC40377
0.5455 Remote Similarity NPC26653
0.5455 Remote Similarity NPC214910
0.5455 Remote Similarity NPC80600
0.5455 Remote Similarity NPC481303
0.5439 Remote Similarity NPC218003
0.5424 Remote Similarity NPC479030
0.5424 Remote Similarity NPC111536
0.5424 Remote Similarity NPC37468
0.5424 Remote Similarity NPC186418
0.5424 Remote Similarity NPC8497
0.541 Remote Similarity NPC264381
0.541 Remote Similarity NPC295970
0.541 Remote Similarity NPC57587
0.54 Remote Similarity NPC152722
0.5397 Remote Similarity NPC185103
0.5385 Remote Similarity NPC69513
0.5385 Remote Similarity NPC145900
0.537 Remote Similarity NPC265442
0.5357 Remote Similarity NPC248355
0.5357 Remote Similarity NPC479029
0.5345 Remote Similarity NPC269421
0.5323 Remote Similarity NPC146837
0.5323 Remote Similarity NPC30432
0.5323 Remote Similarity NPC601944
0.5323 Remote Similarity NPC606353
0.5312 Remote Similarity NPC169761
0.5294 Remote Similarity NPC198798
0.5283 Remote Similarity NPC48863
0.5283 Remote Similarity NPC251981
0.5283 Remote Similarity NPC13745
0.5283 Remote Similarity NPC604209
0.5263 Remote Similarity NPC55040
0.5263 Remote Similarity NPC599943
0.5238 Remote Similarity NPC186406
0.5192 Remote Similarity NPC36434
0.5185 Remote Similarity NPC215833
0.5179 Remote Similarity NPC210015
0.5179 Remote Similarity NPC210478
0.5172 Remote Similarity NPC302378
0.5172 Remote Similarity NPC59324
0.5172 Remote Similarity NPC85799
0.5172 Remote Similarity NPC303422
0.5172 Remote Similarity NPC232673
0.5172 Remote Similarity NPC34456
0.5167 Remote Similarity NPC479374
0.5156 Remote Similarity NPC170475
0.5091 Remote Similarity NPC49074
0.5088 Remote Similarity NPC57751
0.5088 Remote Similarity NPC105827
0.5088 Remote Similarity NPC609351
0.5085 Remote Similarity NPC100389
0.5082 Remote Similarity NPC146803
0.5082 Remote Similarity NPC474044
0.5082 Remote Similarity NPC121001
0.5082 Remote Similarity NPC600107
0.5082 Remote Similarity NPC604892
0.5079 Remote Similarity NPC278329
0.5079 Remote Similarity NPC5029
0.5079 Remote Similarity NPC605700
0.5077 Remote Similarity NPC26195
0.5077 Remote Similarity NPC488085

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC518554 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
0.6122 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