Natural Product: NPC540887

Natural Product IDNPC540887
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-O-a-D-glucopyranosyl-5-hydroxymellein
IUPAC Name (3~{R})-8-hydroxy-3-methyl-5-[3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-isochroman-1-one
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 KJUZOFSYQLKULW-IZIZLXPASA-N
Standard InCHI InChI=1S/C16H20O9/c1-6-4-7-9(3-2-8(18)11(7)15(22)23-6)24-16-14(21)13(20)12(19)10(5-17)25-16/h2-3,6,10,12-14,16-21H,4-5H2,1H3/t6-,10?,12?,13?,14?,16?/m1/s1
SMILES C[C@@H]1CC2=C(OC3OC(CO)C(O)C(O)C3O)C=CC(O)=C2C(=O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.11 Volume:   328.189
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Van der Waals volume.
Dense:   1.085 LogP:   -0.402
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.266
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.679
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   145.91
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Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.416 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.011 Fsp3:   0.562
MCE-18:   71.2
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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:   0.128 Fluc inhibitor:   0.007
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.223
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.335
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.201 Promiscuous compounds:   0.348

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.127 MDCK Permeability:   -5.086
Pgp-inhibitor:   0.0 Pgp-substrate:   0.437
PAMPA:   0.999
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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):   0.664
20% Bioavailability (F20%):   0.315 30% Bioavailability (F30%):   0.921
50% Bioavailability (F50%):   0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.031 MRP1:   0.868
Plasma Protein Binding (PPB):   74.591% Volume Distribution (VD):   -0.129
Fu: 26.107%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.068
OATP1B3 inhibitor:   0.915 BCRP inhibitor:   0.028
BSEP inhibitor:   0.078

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.188 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.064 CYP3A4-substrate:   0.861
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.436
HLM stability:   0.019
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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):  2.489 Half-life (T1/2):  2.343

ADMET: Toxicity

hERG Blockers:  0.024 hERG Blockers (10um):  0.266
Human Hepatotoxicity (H-HT):  0.638 Drug-induced Liver Injury (DILI):  0.832
AMES Toxicity:  0.927 Rat Oral Acute Toxicity:  0.749
Maximum Recommended Daily Dose:  0.582 Skin Sensitization:  0.996
Carcinogencity:  0.477 Eye Corrosion:  0.0
Eye Irritation:  0.157 Respiratory Toxicity:  0.198
Drug-induced Neurotoxicity:  0.679 Ototoxicity:  0.874
Hematotoxicity:  0.077 Drug-induced Nephrotoxicity:  0.769
Genotoxicity:  0.913 RPMI-8226 Immunitoxicity:  0.121
A549 Cytotoxicity:  0.298 Hek293 Cytotoxicity:  0.287
BCF:   0.29
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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:   2.712
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.328
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.437
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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
NPO57316 Aspergillus sp. CMM Genus Aspergillaceae 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 NPC540887 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
0.6 Remote Similarity NPC475628
0.5694 Remote Similarity NPC61594
0.5672 Remote Similarity NPC611586
0.5645 Remote Similarity NPC40377
0.5606 Remote Similarity NPC97326
0.5593 Remote Similarity NPC9248
0.5571 Remote Similarity NPC177742
0.5455 Remote Similarity NPC228907
0.5429 Remote Similarity NPC302989
0.541 Remote Similarity NPC226712
0.541 Remote Similarity NPC608788
0.5345 Remote Similarity NPC142319
0.5278 Remote Similarity NPC92054
0.527 Remote Similarity NPC217950
0.527 Remote Similarity NPC260604
0.5238 Remote Similarity NPC214454
0.5231 Remote Similarity NPC23084
0.5224 Remote Similarity NPC106025
0.5224 Remote Similarity NPC599943
0.5205 Remote Similarity NPC299435
0.52 Remote Similarity NPC56735
0.52 Remote Similarity NPC147596
0.5156 Remote Similarity NPC310661
0.5143 Remote Similarity NPC610808
0.5135 Remote Similarity NPC328093
0.5082 Remote Similarity NPC152722
0.5075 Remote Similarity NPC105827
0.5072 Remote Similarity NPC199335
0.5072 Remote Similarity NPC477240
0.5068 Remote Similarity NPC146837
0.5068 Remote Similarity NPC601828
0.5062 Remote Similarity NPC605563

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC540887 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
0.541 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