Detailed information for compound 1759614

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 389.331 | Formula: C18H14F3N5O2
  • H donors: 2 H acceptors: 3 LogP: 1.87 Rotable bonds: 5
    Rule of 5 violations (Lipinski): 1
  • SMILES: N#Cc1ccc(nc1)C(=O)Nc1ccc(c(c1)[C@@]1(CCOC(=N1)N)C(F)F)F
  • InChi: 1S/C18H14F3N5O2/c19-13-3-2-11(25-15(27)14-4-1-10(8-22)9-24-14)7-12(13)18(16(20)21)5-6-28-17(23)26-18/h1-4,7,9,16H,5-6H2,(H2,23,26)(H,25,27)/t18-/m0/s1
  • InChiKey: ZQBDXEARYNLKKR-SFHVURJKSA-N  

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 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
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsB 0.0314 0.3131 0.4188
Mycobacterium tuberculosis Phenyloxazoline synthase MbtB (phenyloxazoline synthetase) 0.0365 0.3948 0.528
Brugia malayi Beta-ketoacyl synthase, N-terminal domain containing protein 0.0391 0.4361 0.4361
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsA 0.0314 0.3131 0.4188
Mycobacterium ulcerans polyketide synthase Pks9 0.0258 0.2228 0.2981
Mycobacterium ulcerans polyketide synthase 0.0391 0.4361 0.5834
Mycobacterium leprae Probable polyketide synthase Pks1 0.0415 0.4752 0.6337
Mycobacterium ulcerans thioesterase TesA 0.0326 0.3311 0.443
Mycobacterium tuberculosis Probable polyketide synthase Pks15 0.0158 0.061 0.0817
Mycobacterium tuberculosis Probable multifunctional mycocerosic acid synthase membrane-associated Mas 0.0415 0.4752 0.6357
Mycobacterium tuberculosis Probable thioesterase TesA 0.0326 0.3311 0.443
Mycobacterium tuberculosis Probable fatty acid synthase Fas (fatty acid synthetase) 0.0123 0.0042 0.0056
Mycobacterium tuberculosis Probable polyketide synthase Pks5 0.0379 0.4168 0.5576
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSA 0.0391 0.4361 0.581
Mycobacterium tuberculosis Probable polyketide synthase Pks8 0.032 0.3214 0.4299
Mycobacterium ulcerans Type I modular polyketide synthase 0.0391 0.4361 0.5834
Mycobacterium tuberculosis Polyketide synthase Pks2 0.0379 0.4168 0.5576
Mycobacterium tuberculosis Phenolpthiocerol synthesis type-I polyketide synthase PpsC 0.0391 0.4361 0.5834
Loa Loa (eye worm) hypothetical protein 0.0219 0.1592 0.0823
Mycobacterium tuberculosis Probable membrane bound polyketide synthase Pks6 0.0584 0.7476 1
Mycobacterium ulcerans fatty acid synthase Fas 0.0123 0.0042 0.0056
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsD 0.0391 0.4361 0.5834
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSE 0.0258 0.2228 0.2941
Mycobacterium leprae PROBABLE THIOESTERASE TESA 0.0326 0.3311 0.4398
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsE 0.0258 0.2228 0.2981
Mycobacterium tuberculosis Probable polyketide synthase Pks9 0.0222 0.1644 0.2199
Mycobacterium tuberculosis Phenolpthiocerol synthesis type-I polyketide synthase PpsA 0.0391 0.4361 0.5834
Mycobacterium ulcerans thioesterase 0.0326 0.3311 0.443
Mycobacterium tuberculosis Polyketide synthetase MbtC (polyketide synthase) 0.0134 0.0229 0.0306
Toxoplasma gondii type I fatty acid synthase, putative 0.0415 0.4752 1
Mycobacterium tuberculosis Probable polyketide synthase Pks7 0.0415 0.4752 0.6357
Loa Loa (eye worm) hypothetical protein 0.0657 0.8643 1
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSD 0.0391 0.4361 0.581
Mycobacterium leprae Probable multifunctional mycocerosic acid synthase membrane associated enzyme Mas 0.0415 0.4752 0.6337
Mycobacterium ulcerans Type I modular polyketide synthase 0.0391 0.4361 0.5834
Mycobacterium tuberculosis Probable polyketide synthase Pks1 0.0281 0.2588 0.3461
Toxoplasma gondii type I fatty acid synthase, putative 0.0278 0.2547 0.3708
Mycobacterium tuberculosis Phenolpthiocerol synthesis type-I polyketide synthase PpsD 0.0391 0.4361 0.5834
Mycobacterium ulcerans polyketide synthase 0.0415 0.4752 0.6357
Onchocerca volvulus 0.068 0.9025 0.9285
Mycobacterium ulcerans Type I modular polyketide synthase 0.0391 0.4361 0.5834
Loa Loa (eye worm) fatty acid synthase 0.0386 0.4277 0.4318
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSC 0.0415 0.4752 0.6337
Mycobacterium ulcerans polyketide synthase Pks13 0.0584 0.7476 1
Brugia malayi AMP-binding enzyme family protein 0.0365 0.3948 0.3948
Mycobacterium ulcerans multifunctional mycocerosic acid synthase membrane-associated Mas 0.0415 0.4752 0.6357
Loa Loa (eye worm) AMP-binding enzyme family protein 0.0365 0.3948 0.3889
Mycobacterium tuberculosis Polyketide synthase Pks12 0.0415 0.4752 0.6357
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSB 0.0314 0.3131 0.4155
Onchocerca volvulus Fatty acid synthase homolog 0.0704 0.9416 1
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsC 0.0415 0.4752 0.6357
Mycobacterium tuberculosis Polyketide synthase Pks13 0.0584 0.7476 1
Schistosoma mansoni memapsin-2 (A01 family) 0.0521 0.6458 0.5
Mycobacterium leprae Polyketide synthase Pks13 0.0584 0.7476 1
Toxoplasma gondii beta-ketoacyl synthase, N-terminal domain-containing protein 0.0254 0.2149 0.2574

Activities

Activity type Activity value Assay description Source Reference
Activity (functional) = 34 % Reduction of amyloid beta40 level in C57B1/6J mouse brain at 3 mg/kg, po after 4 hrs by AlphaLISA relative to control ChEMBL. 23590342
IC50 (binding) = 46 nM BindingDB_Patents: Inhitbition Assay. 48.5 .mu.L of substrate peptide solution (Biotin-XSEVNLDAEFRHDSGC-Eu: X=.epsilon.-amino-n-capronic acid, Eu=Europium cryptate) was added to each well of 96-hole half-area plate (a black plate: Costar), and after addition of 0.5 .mu.l of the test compound (dissolved in N,N'-dimethyl formaldehyde) and 1 .mu.l of Recombinant human BACE1(R&D Systems), the reaction mixture was incubated at 30.degree. C. for 3 hours. The substrate peptide was synthesized by reacting Cryptate TBPCOOH mono SMP (CIS bio international) with Biotin-XSEVNLDAEFRHDSGC (Peptide Institute, Inc.). The final concentrations of the substrate peptide and Recombinant human BACE1 were adjusted to 18 nmol/L and 7.4 nmol/L, respectively, and the reaction was performed in sodium acetate buffer (50 mmol/L sodium acetate, pH 5.0, 0.008% Triton X-100).After the incubation for reaction, 50 .mu.l of 8.0 .mu.g/ml Streptavidin-XL665 (CIS bio international) dissolved in phosphate buffer. ChEMBL. No reference
IC50 (binding) = 46 nM BindingDB_Patents: Inhitbition Assay. 48.5 .mu.L of substrate peptide solution (Biotin-XSEVNLDAEFRHDSGC-Eu: X=.epsilon.-amino-n-capronic acid, Eu=Europium cryptate) was added to each well of 96-hole half-area plate (a black plate: Costar), and after addition of 0.5 .mu.l of the test compound (dissolved in N,N'-dimethyl formaldehyde) and 1 .mu.l of Recombinant human BACE1(R&D Systems), the reaction mixture was incubated at 30.degree. C. for 3 hours. The substrate peptide was synthesized by reacting Cryptate TBPCOOH mono SMP (CIS bio international) with Biotin-XSEVNLDAEFRHDSGC (Peptide Institute, Inc.). The final concentrations of the substrate peptide and Recombinant human BACE1 were adjusted to 18 nmol/L and 7.4 nmol/L, respectively, and the reaction was performed in sodium acetate buffer (50 mmol/L sodium acetate, pH 5.0, 0.008% Triton X-100).After the incubation for reaction, 50 .mu.l of 8.0 .mu.g/ml Streptavidin-XL665 (CIS bio international) dissolved in phosphate buffer. ChEMBL. No reference
IC50 (binding) = 0.009 uM Inhibition of human BACE1 in HEK293 cells transfected with wild type APP assessed as reduction of amyloid beta40 level after 18 to 20 hrs by AlphaLISA technique ChEMBL. 23590342
IC50 (binding) = 0.054 uM Inhibition of human BACE1 using MR121-labeled substrate incubated for 4 mins prior to substrate addition measured after 2 mins by spectrophotometric analysis ChEMBL. 23590342
Inhibition (binding) = 85 % Inhibition of human ERG channel at 10 uM ChEMBL. 23590342
Ratio IC50 (binding) = 6 Selectivity ratio of IC50 for human BACE1 to IC50 for BACE1 in HEK293 cells ChEMBL. 23590342

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

1 literature reference was collected for this gene.

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