Natural Product: NPC568293

Natural Product IDNPC568293
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3150-20-7
IUPAC Name (2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-(4-methoxyphenoxy)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 SIXFVXJMCGPTRB-KSSYENDESA-N
Standard InCHI InChI=1S/C13H18O7/c1-18-7-2-4-8(5-3-7)19-13-12(17)11(16)10(15)9(6-14)20-13/h2-5,9-17H,6H2,1H3/t9-,10+,11+,12-,13-/m1/s1
SMILES COC1=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:   286.11 Volume:   269.914
?
Van der Waals volume.
Dense:   1.06 LogP:   0.018
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.422
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.208
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   108.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.555 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.197 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:   0.486 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.034
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.032
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.327 Promiscuous compounds:   0.16

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.714 MDCK Permeability:   -4.995
Pgp-inhibitor:   0.0 Pgp-substrate:   0.199
PAMPA:   0.979
?
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):   0.989
20% Bioavailability (F20%):   0.803 30% Bioavailability (F30%):   0.981
50% Bioavailability (F50%):   0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.079 MRP1:   0.269
Plasma Protein Binding (PPB):   62.968% Volume Distribution (VD):   -0.074
Fu: 34.631%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.973
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.012
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.031 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.011
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.835
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):  3.627 Half-life (T1/2):  2.069

ADMET: Toxicity

hERG Blockers:  0.04 hERG Blockers (10um):  0.142
Human Hepatotoxicity (H-HT):  0.687 Drug-induced Liver Injury (DILI):  0.838
AMES Toxicity:  0.951 Rat Oral Acute Toxicity:  0.057
Maximum Recommended Daily Dose:  0.022 Skin Sensitization:  0.998
Carcinogencity:  0.544 Eye Corrosion:  0.005
Eye Irritation:  0.766 Respiratory Toxicity:  0.124
Drug-induced Neurotoxicity:  0.15 Ototoxicity:  0.78
Hematotoxicity:  0.728 Drug-induced Nephrotoxicity:  0.78
Genotoxicity:  0.151 RPMI-8226 Immunitoxicity:  0.113
A549 Cytotoxicity:  0.485 Hek293 Cytotoxicity:  0.228
BCF:   0.372
?
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:   2.767
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.107
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.35
?
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 NPC568293 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
0.7805 Intermediate Similarity NPC153149
0.7619 Intermediate Similarity NPC25817
0.7317 Intermediate Similarity NPC276195
0.7317 Intermediate Similarity NPC212729
0.7317 Intermediate Similarity NPC142319
0.7317 Intermediate Similarity NPC604498
0.7179 Intermediate Similarity NPC228907
0.7143 Intermediate Similarity NPC217854
0.7143 Intermediate Similarity NPC269242
0.7045 Intermediate Similarity NPC609376
0.6977 Remote Similarity NPC192810
0.6977 Remote Similarity NPC294470
0.6739 Remote Similarity NPC221090
0.6667 Remote Similarity NPC60589
0.6667 Remote Similarity NPC469708
0.6667 Remote Similarity NPC604439
0.6596 Remote Similarity NPC166040
0.6531 Remote Similarity NPC479028
0.6531 Remote Similarity NPC479031
0.6522 Remote Similarity NPC200092
0.6444 Remote Similarity NPC152722
0.6383 Remote Similarity NPC80098
0.6383 Remote Similarity NPC145900
0.6327 Remote Similarity NPC218685
0.6304 Remote Similarity NPC299144
0.62 Remote Similarity NPC472024
0.62 Remote Similarity NPC270849
0.62 Remote Similarity NPC23084
0.62 Remote Similarity NPC604356
0.6087 Remote Similarity NPC9248
0.6078 Remote Similarity NPC26653
0.6078 Remote Similarity NPC80600
0.6042 Remote Similarity NPC69513
0.6038 Remote Similarity NPC247146
0.6 Remote Similarity NPC484157
0.5962 Remote Similarity NPC248355
0.5918 Remote Similarity NPC48863
0.5918 Remote Similarity NPC214454
0.5918 Remote Similarity NPC95292
0.5918 Remote Similarity NPC251981
0.5918 Remote Similarity NPC13745
0.5882 Remote Similarity NPC251102
0.5882 Remote Similarity NPC210298
0.5849 Remote Similarity NPC55040
0.5833 Remote Similarity NPC12308
0.5833 Remote Similarity NPC226712
0.5833 Remote Similarity NPC608788
0.5818 Remote Similarity NPC294166
0.5818 Remote Similarity NPC78809
0.5818 Remote Similarity NPC115022
0.58 Remote Similarity NPC310661
0.58 Remote Similarity NPC215833
0.5769 Remote Similarity NPC26080
0.5769 Remote Similarity NPC165686
0.5769 Remote Similarity NPC210478
0.5741 Remote Similarity NPC302378
0.5714 Remote Similarity NPC37468
0.5686 Remote Similarity NPC49074
0.566 Remote Similarity NPC473044
0.566 Remote Similarity NPC479029
0.5577 Remote Similarity NPC162093
0.5577 Remote Similarity NPC83975
0.5577 Remote Similarity NPC606892
0.5556 Remote Similarity NPC25292
0.5556 Remote Similarity NPC104167
0.5536 Remote Similarity NPC276753
0.5536 Remote Similarity NPC205796
0.5517 Remote Similarity NPC210192
0.5517 Remote Similarity NPC175275
0.549 Remote Similarity NPC40377
0.549 Remote Similarity NPC9912
0.5472 Remote Similarity NPC164599
0.5455 Remote Similarity NPC473045
0.5455 Remote Similarity NPC232673
0.5439 Remote Similarity NPC479030
0.5439 Remote Similarity NPC246947
0.5439 Remote Similarity NPC604095
0.5424 Remote Similarity NPC295970
0.537 Remote Similarity NPC57751
0.537 Remote Similarity NPC105827
0.5357 Remote Similarity NPC190714
0.5357 Remote Similarity NPC99515
0.5357 Remote Similarity NPC605646
0.5345 Remote Similarity NPC604892
0.5294 Remote Similarity NPC166168
0.5294 Remote Similarity NPC610709
0.5283 Remote Similarity NPC205054
0.5283 Remote Similarity NPC19470
0.5273 Remote Similarity NPC95392
0.5273 Remote Similarity NPC84013
0.5273 Remote Similarity NPC222455
0.5273 Remote Similarity NPC55715
0.5273 Remote Similarity NPC35877
0.5273 Remote Similarity NPC189589
0.5273 Remote Similarity NPC599943
0.5254 Remote Similarity NPC248119
0.5254 Remote Similarity NPC98777
0.5254 Remote Similarity NPC189115
0.5246 Remote Similarity NPC108674
0.5185 Remote Similarity NPC214910
0.5185 Remote Similarity NPC481303
0.5179 Remote Similarity NPC103409
0.5179 Remote Similarity NPC208769
0.5179 Remote Similarity NPC34456
0.5179 Remote Similarity NPC604162
0.5172 Remote Similarity NPC37074
0.5172 Remote Similarity NPC185778
0.5167 Remote Similarity NPC178851
0.5167 Remote Similarity NPC99233
0.5094 Remote Similarity NPC265442
0.5091 Remote Similarity NPC609351
0.5088 Remote Similarity NPC100389
0.5088 Remote Similarity NPC470236
0.5088 Remote Similarity NPC146540
0.5085 Remote Similarity NPC146803
0.5085 Remote Similarity NPC474044
0.5085 Remote Similarity NPC287780
0.5085 Remote Similarity NPC60982
0.5085 Remote Similarity NPC175976
0.5082 Remote Similarity NPC30432
0.5082 Remote Similarity NPC601944
0.5082 Remote Similarity NPC605700
0.5082 Remote Similarity NPC606849
0.5079 Remote Similarity NPC219163

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC568293 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
0.5833 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