Natural Product: NPC184593

Natural Product IDNPC184593
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1,1-Diethoxyethane
IUPAC Name 1,1-diethoxyethane
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1338583
PubChem CID 7765
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000254] Ethers
          • [CHEMONTID:0001656] Acetals

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 DHKHKXVYLBGOIT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C6H14O2/c1-4-7-6(3)8-5-2/h6H,4-5H2,1-3H3
SMILES CCOC(C)OCC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   118.1 Volume:   129.913
?
Van der Waals volume.
Dense:   0.909 LogP:   0.979
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.745
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.37
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   0.0
TPSA:   18.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.519 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.389 Fsp3:   1.0
MCE-18:   0.0
?
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:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.005 Fluc inhibitor:   0.233
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.003
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.032

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.564 MDCK Permeability:   -4.796
Pgp-inhibitor:   0.788 Pgp-substrate:   0.001
PAMPA:   0.092
?
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):   0.009
20% Bioavailability (F20%):   0.013 30% Bioavailability (F30%):   0.099
50% Bioavailability (F50%):   0.012

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.678 MRP1:   0.808
Plasma Protein Binding (PPB):   10.163% Volume Distribution (VD):   -0.072
Fu: 96.846%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.957
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.069
BSEP inhibitor:   0.958

ADMET: Metabolism

CYP1A2-inhibitor:   0.018 CYP1A2-substrate:   0.413
CYP2C19-inhibitor:   0.99 CYP2C19-substrate:   0.161
CYP2C9-inhibitor:   0.422 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.554 CYP2D6-substrate:   0.011
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.85
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.685
HLM stability:   0.186
?
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):  10.1 Half-life (T1/2):  1.743

ADMET: Toxicity

hERG Blockers:  0.162 hERG Blockers (10um):  0.796
Human Hepatotoxicity (H-HT):  0.047 Drug-induced Liver Injury (DILI):  0.187
AMES Toxicity:  0.244 Rat Oral Acute Toxicity:  0.08
Maximum Recommended Daily Dose:  0.013 Skin Sensitization:  0.437
Carcinogencity:  0.686 Eye Corrosion:  0.981
Eye Irritation:  0.999 Respiratory Toxicity:  0.084
Drug-induced Neurotoxicity:  0.051 Ototoxicity:  0.186
Hematotoxicity:  0.142 Drug-induced Nephrotoxicity:  0.084
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.013
A549 Cytotoxicity:  0.034 Hek293 Cytotoxicity:  0.026
BCF:   0.431
?
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:   1.878
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   2.464
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.12
?
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
NPO15462 Angelica sinensis Species Apiaceae Eukaryota roots purchased from Kiu Shun Trading Ltd., Vancouver, Canada 2000 PMID[16643021]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25538068]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27400088]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36838931]
NPO59106 Vicatia thibetica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36838931]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[37480748]
NPO7255 Pterocarpus indicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23256 Mentha arvensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23256 Mentha arvensis Species Lamiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO23256 Mentha arvensis Species Lamiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7255 Pterocarpus indicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7255 Pterocarpus indicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23256 Mentha arvensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7255 Pterocarpus indicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23256 Mentha arvensis Species Lamiaceae 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
NPO15462 Angelica sinensis Oil n.a. 0.13 n.a. n.a. % PMID[36838931]
NPO59106 Vicatia thibetica Oil n.a. 3.51 n.a. n.a. % PMID[36838931]

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
NPT106 Individual protein Peroxisome proliferator-activated receptor delta Homo sapiens Potency n.a. 16873.4 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 14960.1 nM PubChem BioAssay data set
NPT102 Individual protein Interleukin-8 Homo sapiens Potency n.a. 66824.2 nM PubChem BioAssay data set
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 891.3 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. 1064.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 1188.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 21051.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 66571.8 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
- Rattus norvegicus LD50 = 4570.0 mg/kg ToxVal
- Rattus norvegicus LD50 = 4600.0 mg/kg ToxVal
- Mus musculus LD50 = 2.373559282 mg/kg TOXRIC
- Mus musculus LD50 = 3500.0 mg/kg ToxVal
- Oryctolagus cuniculus LD50 < 3540.0 mg/kg ToxVal
- Oryctolagus cuniculus LD50 > 2360.0 mg/kg ToxVal
- Oryctolagus cuniculus LD50 = 8276.0 mg/kg ToxVal
- Oryctolagus cuniculus LD50 = 3545.0 mg/kg ToxVal

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 NPC184593 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC184593 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