Natural Product: NPC112373

Natural Product IDNPC112373
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Evocarpine
IUPAC Name 1-methyl-2-[(Z)-tridec-7-enyl]quinolin-4-one
Synonyms Evocarpine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1643851
PubChem CID 5319779
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0000056] Quinolones and derivatives
          • [CHEMONTID:0001716] Hydroquinolones

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 GXRKDSSARDBYHW-FPLPWBNLSA-N
Standard InCHI InChI=1S/C23H33NO/c1-3-4-5-6-7-8-9-10-11-12-13-16-20-19-23(25)21-17-14-15-18-22(21)24(20)2/h7-8,14-15,17-19H,3-6,9-13,16H2,1-2H3/b8-7-
SMILES CCCCC/C=CCCCCCCc1cc(=O)c2c(n1C)cccc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   339.26 Volume:   393.219
?
Van der Waals volume.
Dense:   0.863 LogP:   6.378
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.419
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.709
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The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   13.0
TPSA:   22.0
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.354 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.352 Fsp3:   0.522
MCE-18:   11.0
?
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:   0.624 Fluc inhibitor:   0.25
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.271
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.37
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.07 Promiscuous compounds:   0.027

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.961 MDCK Permeability:   -4.704
Pgp-inhibitor:   0.982 Pgp-substrate:   0.013
PAMPA:   0.0
?
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%):   0.015 30% Bioavailability (F30%):   0.069
50% Bioavailability (F50%):   0.803

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.457 MRP1:   1.0
Plasma Protein Binding (PPB):   98.65% Volume Distribution (VD):   0.174
Fu: 0.405%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.01
OATP1B3 inhibitor:   0.69 BCRP inhibitor:   0.795
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.024 CYP2C19-substrate:   0.288
CYP2C9-inhibitor:   0.655 CYP2C9-substrate:   0.968
CYP2D6-inhibitor:   0.164 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.006 CYP2C8-inhibitor:   1.0
HLM stability:   0.925
?
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):  4.612 Half-life (T1/2):  0.35

ADMET: Toxicity

hERG Blockers:  0.631 hERG Blockers (10um):  0.794
Human Hepatotoxicity (H-HT):  0.475 Drug-induced Liver Injury (DILI):  0.011
AMES Toxicity:  0.496 Rat Oral Acute Toxicity:  0.184
Maximum Recommended Daily Dose:  0.639 Skin Sensitization:  0.997
Carcinogencity:  0.232 Eye Corrosion:  0.179
Eye Irritation:  0.822 Respiratory Toxicity:  0.841
Drug-induced Neurotoxicity:  0.194 Ototoxicity:  0.31
Hematotoxicity:  0.096 Drug-induced Nephrotoxicity:  0.697
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.147
A549 Cytotoxicity:  0.873 Hek293 Cytotoxicity:  0.8
BCF:   1.557
?
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:   5.03
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.213
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.012
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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
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[7463094]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[8201313]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[8699182]
NPO16845 Euodia bodinieri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4877 Euodia officinalis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8314 Euodia ruticarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4877 Euodia officinalis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8314 Euodia ruticarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16845 Euodia bodinieri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19935 Evodia rutaecarpa Species Rutaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT171 Cell line MRC5 Homo sapiens Activity = 87.6 % PMID[21106378]
NPT171 Cell line MRC5 Homo sapiens Activity = 94.0 % PMID[21106378]
NPT602 Organism Mycobacterium smegmatis Mycobacterium smegmatis MIC = 5900.0 nM PMID[21106378]
NPT1176 Organism Mycobacterium fortuitum Mycobacterium fortuitum MIC = 2.0 ug.mL-1 PMID[21106378]
NPT1177 Organism Mycobacterium phlei Mycobacterium phlei MIC = 2.0 ug.mL-1 PMID[21106378]

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 NPC112373 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
0.9792 High Similarity NPC289145
0.9388 High Similarity NPC291962
0.875 High Similarity NPC258531
0.875 High Similarity NPC161956
0.875 High Similarity NPC177684
0.875 High Similarity NPC3318
0.5507 Remote Similarity NPC85613

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC112373 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