Natural Product: NPC140151

Natural Product IDNPC140151
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6''-O-Galloylsalidroside
IUPAC Name [(2R,3S,4S,5R,6R)-3,4,5-trihydroxy-6-[2-(4-hydroxyphenyl)ethoxy]oxan-2-yl]methyl 3,4,5-trihydroxybenzoate
Synonyms 6'-O-Galloylsalidroside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1770695
PubChem CID 13270048
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001248] Hydroxybenzoic acid derivatives
            • [CHEMONTID:0001251] Gallic acid and derivatives
              • [CHEMONTID:0003539] Galloyl esters

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 BHUHTEAJYSUNLI-PEVLUNPASA-N
Standard InCHI InChI=1S/C21H24O11/c22-12-3-1-10(2-4-12)5-6-30-21-19(28)18(27)17(26)15(32-21)9-31-20(29)11-7-13(23)16(25)14(24)8-11/h1-4,7-8,15,17-19,21-28H,5-6,9H2/t15-,17-,18+,19-,21-/m1/s1
SMILES Oc1ccc(cc1)CCO[C@@H]1O[C@H](COC(=O)c2cc(O)c(c(c2)O)O)[C@H]([C@@H]([C@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   452.13 Volume:   424.34
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Van der Waals volume.
Dense:   1.065 LogP:   0.323
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.978
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.293
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   19.0
TPSA:   186.37
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   7.0 Rings:   3.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.217 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.771 Fsp3:   0.381
MCE-18:   70.241
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.329 Fluc inhibitor:   0.45
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.067
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.466
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.157 Promiscuous compounds:   0.832

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.488 MDCK Permeability:   -5.146
Pgp-inhibitor:   0.0 Pgp-substrate:   0.09
PAMPA:   0.992
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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):   0.024
20% Bioavailability (F20%):   0.911 30% Bioavailability (F30%):   0.948
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.991
Plasma Protein Binding (PPB):   71.101% Volume Distribution (VD):   -0.25
Fu: 29.341%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.981
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.817
BSEP inhibitor:   0.327

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.57
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.079
?
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):  3.748 Half-life (T1/2):  2.367

ADMET: Toxicity

hERG Blockers:  0.084 hERG Blockers (10um):  0.885
Human Hepatotoxicity (H-HT):  0.128 Drug-induced Liver Injury (DILI):  0.735
AMES Toxicity:  0.558 Rat Oral Acute Toxicity:  0.018
Maximum Recommended Daily Dose:  0.116 Skin Sensitization:  1.0
Carcinogencity:  0.145 Eye Corrosion:  0.001
Eye Irritation:  0.877 Respiratory Toxicity:  0.007
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  0.949
Hematotoxicity:  0.003 Drug-induced Nephrotoxicity:  0.067
Genotoxicity:  0.631 RPMI-8226 Immunitoxicity:  0.011
A549 Cytotoxicity:  0.915 Hek293 Cytotoxicity:  0.432
BCF:   0.595
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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:   3.269
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.604
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.088
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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
NPO5829 Distylium racemosum Species Hamamelidaceae Eukaryota n.a. n.a. n.a. PMID[21489793]
NPO5829 Distylium racemosum Species Hamamelidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5829 Distylium racemosum Species Hamamelidaceae 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
NPT3046 Individual protein Ribonuclease HI Escherichia coli (strain K12) IC50 > 20000.0 nM PMID[20961068]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. IC50 = 1700.0 nM PMID[25280369]
NPT2 Others Unspecified n.a. IC50 = 3500.0 nM PMID[20624681]
NPT2 Others Unspecified n.a. IC50 = 17400.0 nM PMID[21084196]

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 NPC140151 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
0.6833 Remote Similarity NPC92117
0.6286 Remote Similarity NPC288416
0.6164 Remote Similarity NPC34293
0.6053 Remote Similarity NPC472860
0.6053 Remote Similarity NPC484816
0.5968 Remote Similarity NPC157338
0.5942 Remote Similarity NPC84789
0.5797 Remote Similarity NPC479469
0.5714 Remote Similarity NPC484156
0.5694 Remote Similarity NPC471345
0.5694 Remote Similarity NPC90318
0.5676 Remote Similarity NPC287597
0.5616 Remote Similarity NPC485233
0.5467 Remote Similarity NPC475058
0.5443 Remote Similarity NPC289346
0.5342 Remote Similarity NPC166277
0.5303 Remote Similarity NPC266045
0.5281 Remote Similarity NPC195114
0.527 Remote Similarity NPC472859
0.5256 Remote Similarity NPC476017
0.5224 Remote Similarity NPC114096
0.52 Remote Similarity NPC25389
0.5176 Remote Similarity NPC600647
0.5176 Remote Similarity NPC610492
0.5156 Remote Similarity NPC225036
0.5132 Remote Similarity NPC90905
0.5119 Remote Similarity NPC611142
0.5075 Remote Similarity NPC44260
0.5057 Remote Similarity NPC479369

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC140151 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
NPD

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