Natural Product: NPC314084

Natural Product IDNPC314084
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (R)-10-Methyl-6-Undecanolide
IUPAC Name (7R)-7-(4-methylpentyl)oxepan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL467698
PubChem CID 10104200
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000050] Lactones

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 UBMFFGFEUOLSRP-LLVKDONJSA-N
Standard InCHI InChI=1S/C12H22O2/c1-10(2)6-5-8-11-7-3-4-9-12(13)14-11/h10-11H,3-9H2,1-2H3/t11-/m1/s1
SMILES CC(CCC[C@H]1CCCCC(=O)O1)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   198.16 Volume:   222.496
?
Van der Waals volume.
Dense:   0.891 LogP:   3.257
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.937
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.995
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   8.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.648 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.714 Fsp3:   0.917
MCE-18:   14.609
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.037 Fluc inhibitor:   0.087
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.998 Promiscuous compounds:   0.349

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.778 MDCK Permeability:   -4.686
Pgp-inhibitor:   0.534 Pgp-substrate:   0.054
PAMPA:   0.06
?
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):   0.004
20% Bioavailability (F20%):   0.021 30% Bioavailability (F30%):   0.671
50% Bioavailability (F50%):   0.861

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.043 MRP1:   0.675
Plasma Protein Binding (PPB):   47.252% Volume Distribution (VD):   0.016
Fu: 50.457%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.974
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.794
BSEP inhibitor:   0.537

ADMET: Metabolism

CYP1A2-inhibitor:   0.323 CYP1A2-substrate:   0.031
CYP2C19-inhibitor:   0.896 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.038 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.056 CYP2D6-substrate:   0.282
CYP3A4-inhibitor:   0.269 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.009 CYP2C8-inhibitor:   0.862
HLM stability:   0.989
?
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):  5.277 Half-life (T1/2):  0.759

ADMET: Toxicity

hERG Blockers:  0.089 hERG Blockers (10um):  0.376
Human Hepatotoxicity (H-HT):  0.563 Drug-induced Liver Injury (DILI):  0.353
AMES Toxicity:  0.385 Rat Oral Acute Toxicity:  0.077
Maximum Recommended Daily Dose:  0.256 Skin Sensitization:  0.97
Carcinogencity:  0.481 Eye Corrosion:  0.99
Eye Irritation:  0.998 Respiratory Toxicity:  0.258
Drug-induced Neurotoxicity:  0.329 Ototoxicity:  0.154
Hematotoxicity:  0.243 Drug-induced Nephrotoxicity:  0.634
Genotoxicity:  0.003 RPMI-8226 Immunitoxicity:  0.068
A549 Cytotoxicity:  0.063 Hek293 Cytotoxicity:  0.029
BCF:   0.497
?
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:   3.046
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.454
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.662
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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
NPO33479 Streptomycete Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[15043417]
NPO33479 Streptomycete Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[19921834]

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
NPT65 Cell line HepG2 Homo sapiens GI50 = 2.2 ug.mL-1 PMID[15043417]
NPT65 Cell line HepG2 Homo sapiens TGI = 6.8 ug.mL-1 PMID[15043417]
NPT83 Cell line MCF7 Homo sapiens GI50 = 0.11 ug.mL-1 PMID[15043417]
NPT83 Cell line MCF7 Homo sapiens TGI = 4.0 ug.mL-1 PMID[15043417]
NPT83 Cell line MCF7 Homo sapiens GI50 = 0.11 ug.mL-1 PMID[35063731]
NPT65 Cell line HepG2 Homo sapiens GI50 = 0.11 ug.mL-1 PMID[35063731]
NPT4338 Organism Streptomyces viridochromogenes Streptomyces viridochromogenes IZ = 13.0 mm PMID[15043417]
NPT28438 Unchecked Unchecked n.a. GI50 = 0.11 ug.mL-1 PMID[35063731]
NPT79 Organism Bacillus subtilis Bacillus subtilis IZ = 0.0 mm PMID[15043417]
NPT20 Organism Candida albicans Candida albicans IZ = 0.0 mm PMID[15043417]
NPT4340 Organism Chlorella sorokiniana Chlorella sorokiniana IZ = 12.0 mm PMID[15043417]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 2.7 ug.mL-1 PMID[15043417]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. TGI = 6.1 ug.mL-1 PMID[15043417]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus IZ = 0.0 mm PMID[15043417]
NPT19 Organism Escherichia coli Escherichia coli IZ = 0.0 mm PMID[15043417]
NPT4339 Organism Chlorella vulgaris Chlorella vulgaris IZ = 11.0 mm PMID[15043417]
NPT4341 Organism Desmodesmus subspicatus Desmodesmus subspicatus IZ = 11.0 mm PMID[15043417]
NPT176 Organism Artemia salina Artemia salina IZ = 0.0 mm PMID[15043417]
NPT2526 Organism Rhizomucor miehei Rhizomucor miehei IZ = 11.0 mm PMID[15043417]

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 NPC314084 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
0.7931 Intermediate Similarity NPC489810
0.7407 Intermediate Similarity NPC603863
0.6923 Remote Similarity NPC105329
0.6667 Remote Similarity NPC326957
0.6667 Remote Similarity NPC63182
0.6667 Remote Similarity NPC145045
0.6667 Remote Similarity NPC52700
0.6296 Remote Similarity NPC273545
0.5769 Remote Similarity NPC94368
0.5556 Remote Similarity NPC176500
0.5517 Remote Similarity NPC47363
0.5517 Remote Similarity NPC287231

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC314084 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
0.5517 Remote Similarity NPD2699 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