Natural Product: NPC482687

Natural Product IDNPC482687
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 COUZVMMRGYONAQ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 86765296
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0001908] Benzoquinolines
          • [CHEMONTID:0000274] Acridines
            • [CHEMONTID:0001811] Acridones

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 COUZVMMRGYONAQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H17NO5/c1-19(2)7-6-9-13(25-19)8-12(22)14-15(9)20-16-10(17(14)23)4-5-11(21)18(16)24-3/h4-8,21-22H,1-3H3,(H,20,23)
SMILES CC1(C)C=Cc2c(cc(c3c2[nH]c2c(ccc(c2OC)O)c3=O)O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   339.11 Volume:   336.811
?
Van der Waals volume.
Dense:   1.007 LogP:   2.883
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.639
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.364
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   91.78
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.592 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.157 Fsp3:   0.211
MCE-18:   52.174
?
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:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.42 Fluc inhibitor:   0.451
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.678
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.648
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.056 Promiscuous compounds:   0.368

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.074 MDCK Permeability:   -4.764
Pgp-inhibitor:   0.423 Pgp-substrate:   0.186
PAMPA:   0.461
?
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):   0.091
20% Bioavailability (F20%):   0.677 30% Bioavailability (F30%):   0.981
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.037 MRP1:   0.808
Plasma Protein Binding (PPB):   97.584% Volume Distribution (VD):   0.01
Fu: 1.951%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.907
BSEP inhibitor:   0.901

ADMET: Metabolism

CYP1A2-inhibitor:   0.017 CYP1A2-substrate:   0.939
CYP2C19-inhibitor:   0.021 CYP2C19-substrate:   0.106
CYP2C9-inhibitor:   0.397 CYP2C9-substrate:   0.318
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.367
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.674
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.977
HLM stability:   0.796
?
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):  2.612 Half-life (T1/2):  1.462

ADMET: Toxicity

hERG Blockers:  0.166 hERG Blockers (10um):  0.566
Human Hepatotoxicity (H-HT):  0.584 Drug-induced Liver Injury (DILI):  0.662
AMES Toxicity:  0.746 Rat Oral Acute Toxicity:  0.665
Maximum Recommended Daily Dose:  0.585 Skin Sensitization:  0.729
Carcinogencity:  0.665 Eye Corrosion:  0.004
Eye Irritation:  0.934 Respiratory Toxicity:  0.935
Drug-induced Neurotoxicity:  0.528 Ototoxicity:  0.5
Hematotoxicity:  0.403 Drug-induced Nephrotoxicity:  0.679
Genotoxicity:  0.328 RPMI-8226 Immunitoxicity:  0.139
A549 Cytotoxicity:  0.417 Hek293 Cytotoxicity:  0.474
BCF:   1.448
?
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:   4.136
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.414
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.896
?
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
NPO7267 Glycosmis chlorosperma Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[24798019]
NPO7267 Glycosmis chlorosperma Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7267 Glycosmis chlorosperma Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7267 Glycosmis chlorosperma 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
NPT1423 Individual protein Cyclin-dependent kinase 1 Homo sapiens IC50 = 5300.0 nM PMID[24798019]
NPT3240 Individual protein Cyclin-dependent kinase 5 Homo sapiens IC50 = 9000.0 nM PMID[24798019]
NPT1682 Individual protein Dual specificity protein kinase CLK2 Homo sapiens IC50 = 680.0 nM PMID[24798019]
NPT1683 Individual protein Dual specificity protein kinase CLK3 Homo sapiens IC50 = 2300.0 nM PMID[24798019]
NPT3231 Individual protein Dual specificity protein kinase CLK4 Homo sapiens IC50 = 220.0 nM PMID[24798019]
NPT3274 Individual protein Dual specificity tyrosine-phosphorylation-regulated kinase 1B Homo sapiens IC50 = 350.0 nM PMID[24798019]
NPT3399 Individual protein Dual-specificity tyrosine-phosphorylation regulated kinase 2 Homo sapiens IC50 = 1700.0 nM PMID[24798019]
NPT3460 Individual protein Dual-specificity tyrosine-phosphorylation regulated kinase 3 Homo sapiens IC50 = 1200.0 nM PMID[24798019]
NPT1681 Individual protein Dual specificty protein kinase CLK1 Homo sapiens IC50 = 170.0 nM PMID[24798019]
NPT3114 Individual protein Dual-specificity tyrosine-phosphorylation regulated kinase 1A Homo sapiens IC50 = 75.0 nM PMID[24798019]
NPT1682 Individual protein Dual specificity protein kinase CLK2 Homo sapiens IC50 = 680.0 nM PMID[34519506]
NPT3231 Individual protein Dual specificity protein kinase CLK4 Homo sapiens IC50 = 220.0 nM PMID[34519506]
NPT1683 Individual protein Dual specificity protein kinase CLK3 Homo sapiens IC50 > 2000.0 nM PMID[34519506]
NPT1509 Protein complex Cyclin-dependent kinase 5/CDK5 activator 1 Homo sapiens IC50 > 10000.0 nM PMID[24798019]
NPT29648 Single protein Dual specificity protein kinase CLK1 Homo sapiens IC50 = 210.0 nM PMID[34519506]
NPT3932 Individual protein Dual specificity protein kinase CLK1 Mus musculus IC50 = 210.0 nM PMID[24798019]
NPT4092 Protein complex CDK9/cyclin T1 Homo sapiens IC50 = 820.0 nM PMID[24798019]
NPT84 Individual protein Dual specificity tyrosine-phosphorylation-regulated kinase 1A Rattus norvegicus IC50 = 90.0 nM PMID[24798019]
NPT1572 Protein family Glycogen synthase kinase-3 Homo sapiens IC50 = 2000.0 nM PMID[24798019]
NPT4158 Protein complex CDK2/Cyclin A Homo sapiens IC50 = 8200.0 nM PMID[24798019]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT22078 Protein family Glycogen synthase kinase-3 Sus scrofa IC50 = 710.0 nM PMID[24798019]
NPT2 Others Unspecified n.a. IC50 > 10000.0 nM PMID[24798019]
NPT2 Others Unspecified n.a. IC50 = 1100.0 nM PMID[24798019]
NPT2 Others Unspecified n.a. IC50 = 8700.0 nM PMID[24798019]

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 NPC482687 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
0.6923 Remote Similarity NPC218303
0.6567 Remote Similarity NPC288759

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482687 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