Natural Product: NPC315115

Natural Product IDNPC315115
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Hydroxy-3-Methyl-6-(4-Methylpentyl)Pyran-2-One
IUPAC Name 4-hydroxy-3-methyl-6-(4-methylpentyl)pyran-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3087381
PubChem CID 72947654
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000086] Pyrans
        • [CHEMONTID:0000481] Pyranones and derivatives

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 PWPBTWIUAZEBGE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H18O3/c1-8(2)5-4-6-10-7-11(13)9(3)12(14)15-10/h7-8,13H,4-6H2,1-3H3
SMILES CC(CCCc1cc(O)c(c(=O)o1)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   210.13 Volume:   226.013
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Van der Waals volume.
Dense:   0.93 LogP:   3.044
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.972
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.507
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   7.0
TPSA:   50.44
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.831 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.545 Fsp3:   0.583
MCE-18:   8.0
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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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.244 Fluc inhibitor:   0.012
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.037
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.438
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.647 Promiscuous compounds:   0.067

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.683 MDCK Permeability:   -4.513
Pgp-inhibitor:   0.059 Pgp-substrate:   0.012
PAMPA:   0.308
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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):   0.0
20% Bioavailability (F20%):   0.023 30% Bioavailability (F30%):   0.041
50% Bioavailability (F50%):   0.129

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.865 MRP1:   0.976
Plasma Protein Binding (PPB):   96.819% Volume Distribution (VD):   0.14
Fu: 4.077%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.08
OATP1B3 inhibitor:   0.136 BCRP inhibitor:   0.007
BSEP inhibitor:   0.786

ADMET: Metabolism

CYP1A2-inhibitor:   0.899 CYP1A2-substrate:   0.937
CYP2C19-inhibitor:   0.978 CYP2C19-substrate:   0.989
CYP2C9-inhibitor:   0.939 CYP2C9-substrate:   0.029
CYP2D6-inhibitor:   0.044 CYP2D6-substrate:   0.54
CYP3A4-inhibitor:   0.984 CYP3A4-substrate:   0.792
CYP2B6-substrate:   0.139 CYP2C8-inhibitor:   0.999
HLM stability:   0.966
?
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):  5.203 Half-life (T1/2):  0.601

ADMET: Toxicity

hERG Blockers:  0.12 hERG Blockers (10um):  0.56
Human Hepatotoxicity (H-HT):  0.545 Drug-induced Liver Injury (DILI):  0.163
AMES Toxicity:  0.413 Rat Oral Acute Toxicity:  0.387
Maximum Recommended Daily Dose:  0.219 Skin Sensitization:  0.745
Carcinogencity:  0.534 Eye Corrosion:  0.956
Eye Irritation:  0.994 Respiratory Toxicity:  0.77
Drug-induced Neurotoxicity:  0.111 Ototoxicity:  0.234
Hematotoxicity:  0.292 Drug-induced Nephrotoxicity:  0.112
Genotoxicity:  0.05 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.156 Hek293 Cytotoxicity:  0.228
BCF:   1.577
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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:   4.092
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.358
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.868
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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
NPO11517 Streptomyces violascens Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[24182355]
NPO11517 Streptomyces violascens Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[28206772]
NPO11517 Streptomyces violascens Species Streptomycetaceae Bacteria 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
NPT393 Cell line HCT-116 Homo sapiens IC50 > 200000.0 nM PMID[24182355]
NPT165 Cell line HeLa Homo sapiens IC50 > 200000.0 nM PMID[24182355]
NPT65 Cell line HepG2 Homo sapiens IC50 > 200000.0 nM PMID[24182355]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 32.0 ug.mL-1 PMID[24182355]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 200000.0 nM PMID[24182355]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 8.0 ug.mL-1 PMID[24182355]

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 NPC315115 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
0.8462 Intermediate Similarity NPC313444
0.7619 Intermediate Similarity NPC316029
0.7273 Intermediate Similarity NPC316324
0.7273 Intermediate Similarity NPC315394
0.6977 Remote Similarity NPC315597
0.6757 Remote Similarity NPC601792
0.5909 Remote Similarity NPC485076
0.5814 Remote Similarity NPC485075
0.5652 Remote Similarity NPC485077
0.5652 Remote Similarity NPC265050
0.5652 Remote Similarity NPC485078
0.5652 Remote Similarity NPC294618
0.5652 Remote Similarity NPC485079
0.5417 Remote Similarity NPC485068
0.5319 Remote Similarity NPC609414
0.52 Remote Similarity NPC485069
0.5128 Remote Similarity NPC609418
0.5116 Remote Similarity NPC485074
0.5106 Remote Similarity NPC485067
0.5098 Remote Similarity NPC485070
0.5098 Remote Similarity NPC485071
0.5098 Remote Similarity NPC485072

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC315115 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