Natural Product: NPC577357

Natural Product IDNPC577357
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{S},3~{R},4~{S},5~{S},6~{R})-2-[4-[(1~{R},2~{R})-1,2-dihydroxypropyl]phenoxy]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol
IUPAC Name (2~{S},3~{R},4~{S},5~{S},6~{R})-2-[4-[(1~{R},2~{R})-1,2-dihydroxypropyl]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 IVGOVXXPQSIWEF-RUSAUJBJSA-N
Standard InCHI InChI=1S/C15H22O8/c1-7(17)11(18)8-2-4-9(5-3-8)22-15-14(21)13(20)12(19)10(6-16)23-15/h2-5,7,10-21H,6H2,1H3/t7-,10-,11+,12-,13+,14-,15-/m1/s1
SMILES C[C@@H](O)[C@H](O)C1=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:   330.13 Volume:   313.296
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Van der Waals volume.
Dense:   1.054 LogP:   -0.358
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.259
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.976
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   12.0
TPSA:   139.84
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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:   0.375 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.77 Fsp3:   0.6
MCE-18:   51.25
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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:   0.441 Fluc inhibitor:   0.039
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.039
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.022
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.402 Promiscuous compounds:   0.021

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.245 MDCK Permeability:   -4.82
Pgp-inhibitor:   0.0 Pgp-substrate:   0.112
PAMPA:   0.997
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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):   0.067
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.821
50% Bioavailability (F50%):   0.521

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.014 MRP1:   0.02
Plasma Protein Binding (PPB):   44.003% Volume Distribution (VD):   -0.435
Fu: 56.748%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.018
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.008 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.266
HLM stability:   0.034
?
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):  2.224 Half-life (T1/2):  3.575

ADMET: Toxicity

hERG Blockers:  0.01 hERG Blockers (10um):  0.026
Human Hepatotoxicity (H-HT):  0.773 Drug-induced Liver Injury (DILI):  0.489
AMES Toxicity:  0.903 Rat Oral Acute Toxicity:  0.006
Maximum Recommended Daily Dose:  0.005 Skin Sensitization:  0.983
Carcinogencity:  0.155 Eye Corrosion:  0.0
Eye Irritation:  0.191 Respiratory Toxicity:  0.004
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.982
Hematotoxicity:  0.096 Drug-induced Nephrotoxicity:  0.679
Genotoxicity:  0.311 RPMI-8226 Immunitoxicity:  0.092
A549 Cytotoxicity:  0.095 Hek293 Cytotoxicity:  0.074
BCF:   0.242
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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:   2.366
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.87
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.017
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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
NPO49130 Pimpinella anisum L. Genus Apiaceae 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 NPC577357 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
0.7778 Intermediate Similarity NPC294470
0.7727 Intermediate Similarity NPC212729
0.7727 Intermediate Similarity NPC604498
0.7174 Intermediate Similarity NPC269242
0.6939 Remote Similarity NPC200092
0.6735 Remote Similarity NPC60589
0.6735 Remote Similarity NPC469708
0.6735 Remote Similarity NPC609376
0.6471 Remote Similarity NPC80098
0.625 Remote Similarity NPC142319
0.6111 Remote Similarity NPC218685
0.6087 Remote Similarity NPC228907
0.6 Remote Similarity NPC251102
0.6 Remote Similarity NPC210298
0.6 Remote Similarity NPC604356
0.5962 Remote Similarity NPC608788
0.5893 Remote Similarity NPC26080
0.5893 Remote Similarity NPC165686
0.5769 Remote Similarity NPC604439
0.5741 Remote Similarity NPC48863
0.5741 Remote Similarity NPC214454
0.5741 Remote Similarity NPC251981
0.5741 Remote Similarity NPC13745
0.5714 Remote Similarity NPC479028
0.5714 Remote Similarity NPC479031
0.5686 Remote Similarity NPC153149
0.566 Remote Similarity NPC226712
0.56 Remote Similarity NPC276195
0.5577 Remote Similarity NPC25817
0.549 Remote Similarity NPC217854
0.5455 Remote Similarity NPC166040
0.5439 Remote Similarity NPC205054
0.5439 Remote Similarity NPC23084
0.5424 Remote Similarity NPC222455
0.5397 Remote Similarity NPC248119
0.5385 Remote Similarity NPC192810
0.537 Remote Similarity NPC12308
0.5357 Remote Similarity NPC310661
0.5357 Remote Similarity NPC9912
0.5345 Remote Similarity NPC26653
0.5345 Remote Similarity NPC481303
0.5312 Remote Similarity NPC264381
0.5283 Remote Similarity NPC9248
0.5273 Remote Similarity NPC221090
0.5238 Remote Similarity NPC474044
0.5231 Remote Similarity NPC471029
0.5231 Remote Similarity NPC601944
0.5192 Remote Similarity NPC484157
0.5185 Remote Similarity NPC299144
0.5185 Remote Similarity NPC198798
0.5179 Remote Similarity NPC166168
0.5179 Remote Similarity NPC604209
0.5172 Remote Similarity NPC472024
0.5172 Remote Similarity NPC270849
0.5172 Remote Similarity NPC19470
0.5172 Remote Similarity NPC606892
0.5161 Remote Similarity NPC294166
0.5161 Remote Similarity NPC115022
0.5156 Remote Similarity NPC175275
0.5091 Remote Similarity NPC36434
0.5088 Remote Similarity NPC40377
0.5085 Remote Similarity NPC214910
0.5085 Remote Similarity NPC80600
0.5085 Remote Similarity NPC164599
0.5079 Remote Similarity NPC479030
0.5079 Remote Similarity NPC8497
0.5077 Remote Similarity NPC259767
0.5077 Remote Similarity NPC295970

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC577357 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
0.566 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