Natural Product: NPC40377

Natural Product IDNPC40377
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Salirepin
IUPAC Name (2S,3R,4S,5S,6R)-2-[4-hydroxy-2-(hydroxymethyl)phenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms Salirepin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL468146
PubChem CID 16681676
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic glycosides

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 NPNFZOGKIFFKGT-UJPOAAIJSA-N
Standard InCHI InChI=1S/C13H18O8/c14-4-6-3-7(16)1-2-8(6)20-13-12(19)11(18)10(17)9(5-15)21-13/h1-3,9-19H,4-5H2/t9-,10-,11+,12-,13-/m1/s1
SMILES c1cc(c(cc1O)CO)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.1 Volume:   278.704
?
Van der Waals volume.
Dense:   1.084 LogP:   -0.885
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.317
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.1
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 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:   0.378 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.591 Fsp3:   0.538
MCE-18:   49.0
?
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:   0.437 Fluc inhibitor:   0.025
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.038
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.038
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.349 Promiscuous compounds:   0.23

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.452 MDCK Permeability:   -4.953
Pgp-inhibitor:   0.0 Pgp-substrate:   0.018
PAMPA:   0.998
?
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):   0.53
20% Bioavailability (F20%):   0.281 30% Bioavailability (F30%):   0.963
50% Bioavailability (F50%):   0.786

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.086 MRP1:   0.04
Plasma Protein Binding (PPB):   45.752% Volume Distribution (VD):   -0.441
Fu: 55.684%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.001
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.008 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.069
HLM stability:   0.07
?
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):  3.391 Half-life (T1/2):  2.962

ADMET: Toxicity

hERG Blockers:  0.018 hERG Blockers (10um):  0.099
Human Hepatotoxicity (H-HT):  0.603 Drug-induced Liver Injury (DILI):  0.315
AMES Toxicity:  0.825 Rat Oral Acute Toxicity:  0.01
Maximum Recommended Daily Dose:  0.02 Skin Sensitization:  0.986
Carcinogencity:  0.319 Eye Corrosion:  0.0
Eye Irritation:  0.629 Respiratory Toxicity:  0.016
Drug-induced Neurotoxicity:  0.023 Ototoxicity:  0.895
Hematotoxicity:  0.168 Drug-induced Nephrotoxicity:  0.48
Genotoxicity:  0.513 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.07 Hek293 Cytotoxicity:  0.137
BCF:   0.313
?
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:   1.964
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.442
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.801
?
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
NPO9317 Itoa orientalis Species Salicaceae Eukaryota bark, twigs, and leaves n.a. n.a. PMID[18412396]
NPO27632 Idesia polycarpa Species Salicaceae Eukaryota n.a. n.a. n.a. PMID[23628332]
NPO9317 Itoa orientalis Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27632 Idesia polycarpa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9317 Itoa orientalis Species Salicaceae 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
NPT31 Individual protein Cyclooxygenase-2 Homo sapiens Inhibition = 29.7 % PMID[9214736]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT520 Cell line 3T3-L1 Mus musculus IC50 = 110300.0 nM PMID[16180824]

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 NPC40377 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
0.6842 Remote Similarity NPC97326
0.6735 Remote Similarity NPC142319
0.6731 Remote Similarity NPC226712
0.6182 Remote Similarity NPC166168
0.6094 Remote Similarity NPC4958
0.6094 Remote Similarity NPC92054
0.6038 Remote Similarity NPC152722
0.6 Remote Similarity NPC299435
0.5962 Remote Similarity NPC269242
0.5926 Remote Similarity NPC299144
0.5821 Remote Similarity NPC260604
0.5818 Remote Similarity NPC12308
0.5741 Remote Similarity NPC9248
0.566 Remote Similarity NPC484157
0.5652 Remote Similarity NPC145319
0.5645 Remote Similarity NPC475628
0.5634 Remote Similarity NPC474422
0.56 Remote Similarity NPC228907
0.5574 Remote Similarity NPC106025
0.5556 Remote Similarity NPC611586
0.5538 Remote Similarity NPC140722
0.5536 Remote Similarity NPC608788
0.5517 Remote Similarity NPC310661
0.55 Remote Similarity NPC26080
0.55 Remote Similarity NPC165686
0.5472 Remote Similarity NPC212729
0.5472 Remote Similarity NPC604498
0.5469 Remote Similarity NPC610808
0.5455 Remote Similarity NPC177742
0.5439 Remote Similarity NPC221090
0.5397 Remote Similarity NPC199335
0.5397 Remote Similarity NPC477240
0.537 Remote Similarity NPC217854
0.5357 Remote Similarity NPC60589
0.5357 Remote Similarity NPC469708
0.5345 Remote Similarity NPC214454
0.5345 Remote Similarity NPC166040
0.5333 Remote Similarity NPC205054
0.5333 Remote Similarity NPC23084
0.5333 Remote Similarity NPC19470
0.5312 Remote Similarity NPC190217
0.5294 Remote Similarity NPC101116
0.5273 Remote Similarity NPC192810
0.5273 Remote Similarity NPC294470
0.5246 Remote Similarity NPC214910
0.5246 Remote Similarity NPC210015
0.5246 Remote Similarity NPC481303
0.5238 Remote Similarity NPC59324
0.5238 Remote Similarity NPC85799
0.5238 Remote Similarity NPC303422
0.5224 Remote Similarity NPC99233
0.5217 Remote Similarity NPC212099
0.5185 Remote Similarity NPC276195
0.5172 Remote Similarity NPC69513
0.5167 Remote Similarity NPC218685
0.5161 Remote Similarity NPC57751
0.5161 Remote Similarity NPC105827
0.5156 Remote Similarity NPC478871
0.5156 Remote Similarity NPC478870
0.5156 Remote Similarity NPC478872
0.5156 Remote Similarity NPC478873
0.5152 Remote Similarity NPC604892
0.5147 Remote Similarity NPC271385
0.5147 Remote Similarity NPC5029
0.5147 Remote Similarity NPC601828
0.5147 Remote Similarity NPC605700
0.5088 Remote Similarity NPC609376
0.5085 Remote Similarity NPC48863
0.5085 Remote Similarity NPC251981
0.5085 Remote Similarity NPC13745
0.5082 Remote Similarity NPC83975
0.5082 Remote Similarity NPC606892
0.5079 Remote Similarity NPC599943
0.5077 Remote Similarity NPC242028
0.5077 Remote Similarity NPC294166
0.5077 Remote Similarity NPC134260
0.5077 Remote Similarity NPC203230
0.5077 Remote Similarity NPC252169
0.5077 Remote Similarity NPC115022
0.5077 Remote Similarity NPC469661
0.5077 Remote Similarity NPC65530
0.5075 Remote Similarity NPC210192
0.5075 Remote Similarity NPC302989
0.5072 Remote Similarity NPC169248
0.5072 Remote Similarity NPC271479
0.5072 Remote Similarity NPC72649
0.507 Remote Similarity NPC257963

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC40377 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
0.6731 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