Natural Product: NPC289438

Natural Product IDNPC289438
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Bretschneideroside B
IUPAC Name 4-[(2S,3R,4S,5S,6R)-6-[[(2R,3R,4R)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxymethyl]-3,4,5-trihydroxyoxan-2-yl]oxy-3-hydroxybenzaldehyde
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1223634
PubChem CID 46938555
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 HNPKQZLEUUJVIJ-FQXXIRCGSA-N
Standard InCHI InChI=1S/C18H24O12/c19-4-8-1-2-10(9(21)3-8)29-16-14(24)13(23)12(22)11(30-16)5-27-17-15(25)18(26,6-20)7-28-17/h1-4,11-17,20-26H,5-7H2/t11-,12-,13+,14-,15+,16-,17-,18-/m1/s1
SMILES c1cc(c(cc1C=O)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO[C@H]2[C@@H]([C@@](CO)(CO2)O)O)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   432.13 Volume:   389.152
?
Van der Waals volume.
Dense:   1.11 LogP:   -0.632
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.131
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.995
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   18.0
TPSA:   195.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   7.0 Rings:   3.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.214 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.507 Fsp3:   0.611
MCE-18:   79.655
?
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.401 Fluc inhibitor:   0.056
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.093
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.119
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.221 Promiscuous compounds:   0.236

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.411 MDCK Permeability:   -5.185
Pgp-inhibitor:   0.0 Pgp-substrate:   0.143
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):   0.835
20% Bioavailability (F20%):   0.213 30% Bioavailability (F30%):   0.988
50% Bioavailability (F50%):   0.893

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.02 MRP1:   0.052
Plasma Protein Binding (PPB):   48.096% Volume Distribution (VD):   -0.503
Fu: 56.378%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.01
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 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:   0.012
HLM stability:   0.0
?
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):  2.021 Half-life (T1/2):  2.981

ADMET: Toxicity

hERG Blockers:  0.014 hERG Blockers (10um):  0.084
Human Hepatotoxicity (H-HT):  0.525 Drug-induced Liver Injury (DILI):  0.487
AMES Toxicity:  0.939 Rat Oral Acute Toxicity:  0.013
Maximum Recommended Daily Dose:  0.04 Skin Sensitization:  0.996
Carcinogencity:  0.283 Eye Corrosion:  0.001
Eye Irritation:  0.744 Respiratory Toxicity:  0.022
Drug-induced Neurotoxicity:  0.017 Ototoxicity:  0.868
Hematotoxicity:  0.105 Drug-induced Nephrotoxicity:  0.475
Genotoxicity:  0.464 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.348 Hek293 Cytotoxicity:  0.335
BCF:   0.227
?
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:   2.688
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.48
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.551
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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
NPO1813 Bretschneidera sinensis Species Akaniaceae Eukaryota stems Jiujiang, Jiangxi Province, China 2008-AUG PMID[20722446]
NPO1813 Bretschneidera sinensis Species Akaniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1813 Bretschneidera sinensis Species Akaniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1813 Bretschneidera sinensis Species Akaniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1813 Bretschneidera sinensis Species Akaniaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT937 Cell line NCI-H446 Homo sapiens IC50 > 100.0 ug.mL-1 PMID[20722446]
NPT116 Cell line HL-60 Homo sapiens IC50 > 100.0 ug.mL-1 PMID[20722446]
NPT393 Cell line HCT-116 Homo sapiens IC50 > 100.0 ug.mL-1 PMID[20722446]
NPT937 Cell line NCI-H446 Homo sapiens GI = 38.43 % PMID[20722446]
NPT116 Cell line HL-60 Homo sapiens GI = 7.25 % PMID[20722446]
NPT393 Cell line HCT-116 Homo sapiens GI = 0.0 % PMID[20722446]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100.0 ug.mL-1 PMID[20722446]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI = 0.0 % PMID[20722446]

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 NPC289438 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
0.7015 Intermediate Similarity NPC227980
0.7 Intermediate Similarity NPC602810
0.6716 Remote Similarity NPC287429
0.6667 Remote Similarity NPC212748
0.6364 Remote Similarity NPC171533
0.6197 Remote Similarity NPC25821
0.6164 Remote Similarity NPC34965
0.6111 Remote Similarity NPC242756
0.6027 Remote Similarity NPC23253
0.5946 Remote Similarity NPC470510
0.5811 Remote Similarity NPC6836
0.5658 Remote Similarity NPC470881
0.5556 Remote Similarity NPC473867
0.5513 Remote Similarity NPC252833
0.5467 Remote Similarity NPC473924
0.5316 Remote Similarity NPC476442
0.5316 Remote Similarity NPC215512
0.527 Remote Similarity NPC90318
0.52 Remote Similarity NPC476448
0.52 Remote Similarity NPC469548
0.52 Remote Similarity NPC476445
0.5195 Remote Similarity NPC195196
0.5185 Remote Similarity NPC229687
0.5185 Remote Similarity NPC602634
0.5143 Remote Similarity NPC57751
0.5143 Remote Similarity NPC264784
0.5128 Remote Similarity NPC164172
0.5079 Remote Similarity NPC219040

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC289438 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