Natural Product: NPC482797

Natural Product IDNPC482797
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 OPYPWMGWBUCOSQ-RZNLEFLGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 127035633
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003487] Cyclic ketones
              • [CHEMONTID:0004325] Cyclohexenones

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 OPYPWMGWBUCOSQ-RZNLEFLGSA-N
Standard InCHI InChI=1S/C17H24O6/c1-15(20,7-18)10-3-4-16(2)11(10)5-9-13(23-16)12-6-17(21,8-22-12)14(9)19/h10-12,18,20-21H,3-8H2,1-2H3/t10-,11+,12+,15-,16-,17-/m1/s1
SMILES C[C@@](CO)([C@@H]1CC[C@]2(C)[C@H]1CC1=C([C@@H]3C[C@@](CO3)(C1=O)O)O2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   324.16 Volume:   315.831
?
Van der Waals volume.
Dense:   1.026 LogP:   1.053
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.497
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.849
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.676 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.966 Fsp3:   0.824
MCE-18:   71.419
?
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:   0.037 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.259 Promiscuous compounds:   0.685

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.042 MDCK Permeability:   -4.671
Pgp-inhibitor:   0.002 Pgp-substrate:   0.981
PAMPA:   0.991
?
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):   0.019
20% Bioavailability (F20%):   0.668 30% Bioavailability (F30%):   0.723
50% Bioavailability (F50%):   0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.04 MRP1:   0.822
Plasma Protein Binding (PPB):   36.484% Volume Distribution (VD):   0.083
Fu: 63.082%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.905 BCRP inhibitor:   0.306
BSEP inhibitor:   0.33

ADMET: Metabolism

CYP1A2-inhibitor:   0.013 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.526 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.013
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):  3.037 Half-life (T1/2):  2.533

ADMET: Toxicity

hERG Blockers:  0.014 hERG Blockers (10um):  0.05
Human Hepatotoxicity (H-HT):  0.923 Drug-induced Liver Injury (DILI):  0.706
AMES Toxicity:  0.956 Rat Oral Acute Toxicity:  0.458
Maximum Recommended Daily Dose:  0.758 Skin Sensitization:  0.999
Carcinogencity:  0.987 Eye Corrosion:  0.002
Eye Irritation:  0.762 Respiratory Toxicity:  0.067
Drug-induced Neurotoxicity:  0.474 Ototoxicity:  0.393
Hematotoxicity:  0.658 Drug-induced Nephrotoxicity:  0.983
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.246
A549 Cytotoxicity:  0.457 Hek293 Cytotoxicity:  0.555
BCF:   0.484
?
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:   3.186
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.754
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.817
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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
NPO40151 Guignardia sp. Species Phyllostictaceae Eukaryota n.a. n.a. n.a. PMID[26577190]
NPO40151 Guignardia sp. Species Phyllostictaceae 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
NPT20 Organism Candida albicans Candida albicans MIC80 = 57.3 ug.mL-1 PMID[26577190]
NPT20 Organism Candida albicans Candida albicans MIC80 = 6.3 ug.mL-1 PMID[26577190]
NPT20 Organism Candida albicans Candida albicans Ratio = 0.11 n.a. PMID[26577190]
NPT20 Organism Candida albicans Candida albicans Ratio < 0.25 n.a. PMID[26577190]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC > 100.0 ug.mL-1 PMID[26577190]
NPT20 Organism Candida albicans Candida albicans FC > 16.0 n.a. PMID[26577190]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 79.2 ug.mL-1 PMID[26577190]
NPT19 Organism Escherichia coli Escherichia coli MIC = 78.0 ug.mL-1 PMID[26577190]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 100.0 ug.mL-1 PMID[26577190]

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 NPC482797 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
1.0 High Similarity NPC482798
0.8958 High Similarity NPC101018
0.7736 Intermediate Similarity NPC99760
0.6491 Remote Similarity NPC482793
0.6429 Remote Similarity NPC611467
0.5833 Remote Similarity NPC482794

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482797 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