Natural Product: NPC196246

Natural Product IDNPC196246
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1-O-Butyl 2-O-(2-Ethylhexyl) Benzene-1,2-Dicarboxylate
IUPAC Name 1-O-butyl 2-O-(2-ethylhexyl) benzene-1,2-dicarboxylate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3188746
PubChem CID 6818
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001350] Benzoic acid esters

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 AVOLBYOSCILFLL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H30O4/c1-4-7-11-16(6-3)15-24-20(22)18-13-10-9-12-17(18)19(21)23-14-8-5-2/h9-10,12-13,16H,4-8,11,14-15H2,1-3H3
SMILES CCCCC(CC)COC(=O)c1ccccc1C(=O)OCCCC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   334.21 Volume:   367.898
?
Van der Waals volume.
Dense:   0.908 LogP:   5.792
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.171
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.61
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   13.0 Rigid Bonds:   8.0
TPSA:   52.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.421 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.495 Fsp3:   0.6
MCE-18:   16.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.197 Fluc inhibitor:   0.342
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.031
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.073
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.846 Promiscuous compounds:   0.008

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.947 MDCK Permeability:   -4.698
Pgp-inhibitor:   0.233 Pgp-substrate:   0.018
PAMPA:   0.007
?
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):   0.014
20% Bioavailability (F20%):   0.662 30% Bioavailability (F30%):   0.863
50% Bioavailability (F50%):   0.827

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.909 MRP1:   0.993
Plasma Protein Binding (PPB):   97.615% Volume Distribution (VD):   0.738
Fu: 2.485%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.098
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.15
BSEP inhibitor:   0.932

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.038 CYP2C19-substrate:   0.798
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.033
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.758
CYP3A4-inhibitor:   0.921 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.976
HLM stability:   0.979
?
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):  6.336 Half-life (T1/2):  0.283

ADMET: Toxicity

hERG Blockers:  0.417 hERG Blockers (10um):  0.92
Human Hepatotoxicity (H-HT):  0.024 Drug-induced Liver Injury (DILI):  0.295
AMES Toxicity:  0.017 Rat Oral Acute Toxicity:  0.03
Maximum Recommended Daily Dose:  0.087 Skin Sensitization:  0.74
Carcinogencity:  0.534 Eye Corrosion:  0.264
Eye Irritation:  0.992 Respiratory Toxicity:  0.067
Drug-induced Neurotoxicity:  0.101 Ototoxicity:  0.077
Hematotoxicity:  0.004 Drug-induced Nephrotoxicity:  0.023
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.096 Hek293 Cytotoxicity:  0.27
BCF:   1.672
?
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:   4.239
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.664
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.771
?
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
NPO28243 Canarium schweinfurthii Species Burseraceae Eukaryota Fruits Edem-ani community of Nsukka local government area (LGA), Enugu State, South-east of Nigeria n.a. PMID[35717414]
NPO28243 Canarium schweinfurthii Species Burseraceae Eukaryota n.a. n.a. n.a. PMID[38878840]
NPO28243 Canarium schweinfurthii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16841 Elsholtzia bodinieri Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16841 Elsholtzia bodinieri Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16841 Elsholtzia bodinieri Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28243 Canarium schweinfurthii Species Burseraceae 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
NPO28243 Canarium schweinfurthii n.a. n.a. 0.36 n.a. n.a. % PMID[38878840]

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
NPT74 Individual protein Proto-oncogene c-JUN Homo sapiens Potency n.a. 15488.3 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency n.a. 54482.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 489.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 34376.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 43651.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 21877.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 68589.6 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 24336.5 nM PubChem BioAssay data set

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 NPC196246 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
0.8649 High Similarity NPC305912
0.8649 High Similarity NPC1082
0.7027 Intermediate Similarity NPC10251
0.6667 Remote Similarity NPC604461
0.6429 Remote Similarity NPC270699
0.6341 Remote Similarity NPC93084
0.6341 Remote Similarity NPC251854
0.6341 Remote Similarity NPC601045
0.6341 Remote Similarity NPC603091
0.6279 Remote Similarity NPC603245
0.587 Remote Similarity NPC604244
0.5833 Remote Similarity NPC72977
0.5641 Remote Similarity NPC214067
0.5283 Remote Similarity NPC153053
0.5238 Remote Similarity NPC608938

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC196246 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
0.7027 Intermediate Similarity NPD2182 Pre-clinical
0.5417 Remote Similarity NPD2670 Phase 4

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