Detailed information for compound 1949382

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 423.801 | Formula: C18H16ClF2N5O3
  • H donors: 2 H acceptors: 3 LogP: 2.1 Rotable bonds: 6
    Rule of 5 violations (Lipinski): 1
  • SMILES: COc1cnc(nc1)C(=O)Nc1ccc(c(c1)[C@]1(N=C(N)O[C@H]2[C@@H]1C2)C(F)F)Cl
  • InChi: 1S/C18H16ClF2N5O3/c1-28-9-6-23-14(24-7-9)15(27)25-8-2-3-12(19)10(4-8)18(16(20)21)11-5-13(11)29-17(22)26-18/h2-4,6-7,11,13,16H,5H2,1H3,(H2,22,26)(H,25,27)/t11-,13+,18+/m0/s1
  • InChiKey: VIVKCZYKKIXBRZ-WHWRDJHUSA-N  


Substructure search Similarity search

Network

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Synonyms

No synonyms found for this compound

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Homo sapiens beta-site APP-cleaving enzyme 1 Starlite/ChEMBL No references

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Schistosoma japonicum ko:K07747 beta-site APP-cleaving enzyme 2 (memapsin 1) [EC3.4.23.45], putative Get druggable targets OG5_135830 All targets in OG5_135830
Schistosoma mansoni memapsin-2 (A01 family) Get druggable targets OG5_135830 All targets in OG5_135830
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Plasmodium falciparum plasmepsin VII beta-site APP-cleaving enzyme 1 401 aa 352 aa 21.3 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Onchocerca volvulus Matrilysin homolog 0.0116 0 0.5
Loa Loa (eye worm) angiotensin-converting enzyme family protein 0.0529 1 1
Onchocerca volvulus Matrix metalloproteinase homolog 0.0116 0 0.5
Wolbachia endosymbiont of Brugia malayi extracellular metallopeptidase 0.0258 0.3435 0.5
Echinococcus granulosus matrix metallopeptidase 7 M10 family 0.0191 0.1799 0.5
Echinococcus multilocularis matrix metallopeptidase 7 (M10 family) 0.0191 0.1799 0.5
Loa Loa (eye worm) matrixin family protein 0.0127 0.0254 0.0254
Schistosoma mansoni memapsin-2 (A01 family) 0.0521 0.9796 0.5

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 87.3 nM BindingDB_Patents: Fluorescence Resonance Energy Transfer Assay. The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm). ChEMBL. No reference
IC50 (binding) = 87.3 nM BindingDB_Patents: Fluorescence Resonance Energy Transfer Assay. The assay buffer used in this screen is 0.05 M acetate, pH 4.2, 10% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.2 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 425 nm). ChEMBL. No reference
IC50 (binding) = 374140 nM BindingDB_Patents: Fluorescence Resonance Energy Transfer Assay. Recombinant Cat D was expressed in CHO cells. The assay buffer for CathepsinD is 0.05 M citrate pH 3.5, 10% DMSO final, 5 mM CHAPS. The Cat D enzyme (9 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, is added thereto. The assays are effectively started by the addition of different FRET substrates (20 nM for Cat D) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. The Cat D substrate peptide sequence is based on sequence #1 of Table 1 from Gulnik et al. FEBS Letters v413 p379-384 1997. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (Cat D excitation 500 nm and emission 580 nm). ChEMBL. No reference
IC50 (binding) = 374140 nM BindingDB_Patents: Fluorescence Resonance Energy Transfer Assay. Recombinant Cat D was expressed in CHO cells. The assay buffer for CathepsinD is 0.05 M citrate pH 3.5, 10% DMSO final, 5 mM CHAPS. The Cat D enzyme (9 nM) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, is added thereto. The assays are effectively started by the addition of different FRET substrates (20 nM for Cat D) and the combination is incubated for one hour. The FRET assay is terminated with by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. The Cat D substrate peptide sequence is based on sequence #1 of Table 1 from Gulnik et al. FEBS Letters v413 p379-384 1997. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (Cat D excitation 500 nm and emission 580 nm). ChEMBL. No reference

Phenotypes

Whole-cell/tissue/organism interactions

We have no records of whole-cell/tissue assays done with this compound What does this mean?

Many chemical entities in TDR Targets come from high-throughput screenings with whole cells or tissue samples, and not all assayed compounds have been tested against a single a single target protein, probably because they get ruled out during screening process. Even if these compounds may have not been of interest in the original screening, they may come as interesting leads for other screening assays. Furthermore, we may be able to propose drug-target associations using chemical similarities and network patterns.

Annotated phenotypes:

We have no manually annotated phenotypes for this drug. What does this mean? / Care to help?
In TDR Targets, information about phenotypes that are caused by drugs, or by genetic manipulation of cells (e.g. gene knockouts or knockdowns) is manually curated from the literature. These descriptions help to describe the potential of the target for drug development. If no information is available for this gene or if the information is incomplete, this may mean that i) the papers containing this information either appeared after the curation effort for this organism was carried out or they were inadvertently missed by curators; or that ii) the curation effort for this organism has not yet started.
 
In any case, if you have information about papers containing relevant validation data for this target, please log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.

External resources for this compound

Bibliographic References

No literature references available for this target.

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