Natural Product: NPC283152

Natural Product IDNPC283152
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-(3-Methylbut-2-Enyl)-4-(3-Methylbut-2-Enyloxy)Quinolin-2-Ol
IUPAC Name 4-(3-methylbut-2-enoxy)-3-(3-methylbut-2-enyl)-1H-quinolin-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL444821
PubChem CID 4556
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0000056] Quinolones and derivatives

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 YADLZLRNLRNTCM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H23NO2/c1-13(2)9-10-16-18(22-12-11-14(3)4)15-7-5-6-8-17(15)20-19(16)21/h5-9,11H,10,12H2,1-4H3,(H,20,21)
SMILES CC(=CCc1c(c2ccccc2nc1O)OCC=C(C)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   297.17 Volume:   330.189
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Van der Waals volume.
Dense:   0.9 LogP:   4.885
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.014
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.914
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   13.0
TPSA:   42.35
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.806 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.732 Fsp3:   0.316
MCE-18:   13.0
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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:   1 PAINS Alert:   0
Colloidal aggregators:   0.987 Fluc inhibitor:   0.352
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.816
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.539
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.079 Promiscuous compounds:   0.155

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.67 MDCK Permeability:   -4.651
Pgp-inhibitor:   0.023 Pgp-substrate:   0.141
PAMPA:   0.721
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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):   0.498
20% Bioavailability (F20%):   1.0 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.417
Plasma Protein Binding (PPB):   94.369% Volume Distribution (VD):   0.294
Fu: 4.957%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.79 BCRP inhibitor:   0.995
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.017 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.988 CYP2C19-substrate:   0.912
CYP2C9-inhibitor:   0.811 CYP2C9-substrate:   0.025
CYP2D6-inhibitor:   0.992 CYP2D6-substrate:   0.098
CYP3A4-inhibitor:   0.69 CYP3A4-substrate:   0.993
CYP2B6-substrate:   0.03 CYP2C8-inhibitor:   0.998
HLM stability:   0.999
?
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):  4.755 Half-life (T1/2):  0.874

ADMET: Toxicity

hERG Blockers:  0.102 hERG Blockers (10um):  0.537
Human Hepatotoxicity (H-HT):  0.588 Drug-induced Liver Injury (DILI):  0.29
AMES Toxicity:  0.52 Rat Oral Acute Toxicity:  0.675
Maximum Recommended Daily Dose:  0.272 Skin Sensitization:  0.968
Carcinogencity:  0.453 Eye Corrosion:  0.001
Eye Irritation:  0.605 Respiratory Toxicity:  0.932
Drug-induced Neurotoxicity:  0.631 Ototoxicity:  0.406
Hematotoxicity:  0.287 Drug-induced Nephrotoxicity:  0.689
Genotoxicity:  0.463 RPMI-8226 Immunitoxicity:  0.043
A549 Cytotoxicity:  0.081 Hek293 Cytotoxicity:  0.19
BCF:   2.123
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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:   4.77
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.117
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.787
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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
NPO29389 Haplophyllum tuberculatum Species Rutaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)82500-5]
NPO29980 Euodia roxburghiana Species Rutaceae Eukaryota n.a. Thailand n.a. PMID[11430019]
NPO29980 Euodia roxburghiana Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[8778237]
NPO22061 Siphonaria normalis Species Siphonariidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23807 Trollius macropetalus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29389 Haplophyllum tuberculatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20762 Haplophyllum bucharicum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23807 Trollius macropetalus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23807 Trollius macropetalus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23807 Trollius macropetalus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23807 Trollius macropetalus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22061 Siphonaria normalis Species Siphonariidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29389 Haplophyllum tuberculatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23482 Vernonia cinerascens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23943 Aconitum chiisanense Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24349 Ceratocystis variospora Species Ceratocystidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24233 Thynnus thynnus Species Tiphiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20762 Haplophyllum bucharicum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13435 Propylea quatuordecimpunctata Species Coccinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14209 Dysphania graveolens Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24201 Cinnamomum massoia Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14890 Macroclinidium robustum 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
NPT459 Individual protein Human immunodeficiency virus type 1 reverse transcriptase Human immunodeficiency virus 1 IC50 = 8000.0 nM PMID[8778237]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT404 Cell line CCRF-CEM Homo sapiens CC50 = 71170.0 nM PMID[20350812]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 1640.0 nM PMID[8778237]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 IC50 = 26900.0 nM PMID[8778237]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 IC50 = 3800.0 nM PMID[20350812]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 Inhibition = 87.52 % PMID[20350812]

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 NPC283152 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
0.5246 Remote Similarity NPC288943

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC283152 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