Natural Product: NPC252860

Natural Product IDNPC252860
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Chrysanthemic Acid, Ethyl Ester
IUPAC Name ethyl 2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carboxylate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1596099
PubChem CID 7334
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001549] Monoterpenoids
          • [CHEMONTID:0001563] Monocyclic monoterpenoids

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 VIMXTGUGWLAOFZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H20O2/c1-6-14-11(13)10-9(7-8(2)3)12(10,4)5/h7,9-10H,6H2,1-5H3
SMILES CCOC(=O)C1C(C1(C)C)C=C(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   196.15 Volume:   219.859
?
Van der Waals volume.
Dense:   0.892 LogP:   3.947
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.398
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.641
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   5.0
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:   0.512 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.187 Fsp3:   0.75
MCE-18:   22.857
?
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:   0.029 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.001
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.01
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.728 Promiscuous compounds:   0.151

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.725 MDCK Permeability:   -4.793
Pgp-inhibitor:   0.427 Pgp-substrate:   0.008
PAMPA:   0.205
?
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):   0.037
20% Bioavailability (F20%):   0.576 30% Bioavailability (F30%):   0.63
50% Bioavailability (F50%):   0.961

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.321 MRP1:   0.886
Plasma Protein Binding (PPB):   58.476% Volume Distribution (VD):   0.055
Fu: 40.624%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.017
BSEP inhibitor:   0.932

ADMET: Metabolism

CYP1A2-inhibitor:   0.144 CYP1A2-substrate:   0.943
CYP2C19-inhibitor:   0.614 CYP2C19-substrate:   0.167
CYP2C9-inhibitor:   0.019 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   0.056
CYP3A4-inhibitor:   0.886 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.336 CYP2C8-inhibitor:   0.758
HLM stability:   0.973
?
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):  9.258 Half-life (T1/2):  0.858

ADMET: Toxicity

hERG Blockers:  0.088 hERG Blockers (10um):  0.525
Human Hepatotoxicity (H-HT):  0.292 Drug-induced Liver Injury (DILI):  0.344
AMES Toxicity:  0.284 Rat Oral Acute Toxicity:  0.311
Maximum Recommended Daily Dose:  0.223 Skin Sensitization:  0.297
Carcinogencity:  0.523 Eye Corrosion:  0.245
Eye Irritation:  0.95 Respiratory Toxicity:  0.447
Drug-induced Neurotoxicity:  0.333 Ototoxicity:  0.318
Hematotoxicity:  0.13 Drug-induced Nephrotoxicity:  0.175
Genotoxicity:  0.061 RPMI-8226 Immunitoxicity:  0.023
A549 Cytotoxicity:  0.024 Hek293 Cytotoxicity:  0.098
BCF:   2.445
?
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:   4.152
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.312
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.535
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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
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. PMID[ 21030913]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. leaf n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. flower n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. stem n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. PMID[6387056]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10506 Artemisia apiacea Species Asteraceae 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

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
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 89.36 % PMID[23571415]
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 83.17 % PMID[23571415]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency = 1000.0 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 = 2600.0 mg/kg ToxVal
- Mus musculus LD50 = 2600.0 mg/kg ToxVal
- Mus musculus LD50 > 5000.0 mg/kg ToxVal
- Cavia porcellus LD50 = 1900.0 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 NPC252860 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 NPC252860 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