Detailed information for compound 2019534

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 573.598 | Formula: C33H27N5O5
  • H donors: 1 H acceptors: 4 LogP: 5.3 Rotable bonds: 9
    Rule of 5 violations (Lipinski): 2
  • SMILES: COc1cc2c(ccnc2cc1OC)Oc1ccc(nc1)NC(=O)c1c(c2ccccc2)n(n(c1=O)c1ccccc1)C
  • InChi: 1S/C33H27N5O5/c1-37-31(21-10-6-4-7-11-21)30(33(40)38(37)22-12-8-5-9-13-22)32(39)36-29-15-14-23(20-35-29)43-26-16-17-34-25-19-28(42-3)27(41-2)18-24(25)26/h4-20H,1-3H3,(H,35,36,39)
  • InChiKey: PVNWAPAWLNSQHB-UHFFFAOYSA-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 eukaryotic translation initiation factor 2-alpha kinase 1 Starlite/ChEMBL References
Homo sapiens eukaryotic translation initiation factor 2-alpha kinase 3 Starlite/ChEMBL References
Homo sapiens eukaryotic translation initiation factor 2 alpha kinase 4 Starlite/ChEMBL References
Homo sapiens B-Raf proto-oncogene, serine/threonine kinase Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Brugia malayi Raf kinase Get druggable targets OG5_130459 All targets in OG5_130459
Trypanosoma brucei gambiense protein kinase, putative Get druggable targets OG5_130490 All targets in OG5_130490
Echinococcus multilocularis eukaryotic translation initiation factor 2 alpha Get druggable targets OG5_130490 All targets in OG5_130490
Loa Loa (eye worm) PEK/PEK protein kinase Get druggable targets OG5_133221 All targets in OG5_133221
Trypanosoma congolense protein kinase, putative Get druggable targets OG5_130490 All targets in OG5_130490
Leishmania major protein kinase, putative Get druggable targets OG5_130490 All targets in OG5_130490
Babesia bovis Ser/Thr protein kinase, putative Get druggable targets OG5_129525 All targets in OG5_129525
Trypanosoma congolense protein kinase, putative Get druggable targets OG5_130490 All targets in OG5_130490
Schistosoma mansoni protein kinase Get druggable targets OG5_133221 All targets in OG5_133221
Trypanosoma brucei eukaryotic translation initiation factor 2-alpha kinase 1, putative Get druggable targets OG5_130490 All targets in OG5_130490
Loa Loa (eye worm) TKL/RAF/RAF protein kinase Get druggable targets OG5_130459 All targets in OG5_130459
Brugia malayi Protein kinase domain containing protein Get druggable targets OG5_133221 All targets in OG5_133221
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_129525 All targets in OG5_129525
Schistosoma japonicum ko:K04365 B-Raf proto-oncogene serine/threonine-protein kinase, putative Get druggable targets OG5_130459 All targets in OG5_130459
Loa Loa (eye worm) raf kinase Get druggable targets OG5_130459 All targets in OG5_130459
Brugia malayi RWD domain containing protein Get druggable targets OG5_129525 All targets in OG5_129525
Echinococcus granulosus eukaryotic translation initiation factor 2 alpha Get druggable targets OG5_130490 All targets in OG5_130490
Candida albicans hypothetical protein Get druggable targets OG5_129525 All targets in OG5_129525
Brugia malayi hypothetical protein Get druggable targets OG5_130490 All targets in OG5_130490
Echinococcus granulosus raf serine:threonine protein kinase Get druggable targets OG5_130459 All targets in OG5_130459
Entamoeba histolytica protein kinase domain containing protein Get druggable targets OG5_130490 All targets in OG5_130490
Echinococcus multilocularis eukaryotic translation initiation factor 2 alpha Get druggable targets OG5_129525 All targets in OG5_129525
Leishmania braziliensis protein kinase Get druggable targets OG5_130490 All targets in OG5_130490
Schistosoma mansoni serine/threonine protein kinase Get druggable targets OG5_130459 All targets in OG5_130459
Schistosoma mansoni protein kinase Get druggable targets OG5_133221 All targets in OG5_133221
Leishmania donovani protein kinase, putative Get druggable targets OG5_130490 All targets in OG5_130490
Candida albicans likely protein kinase similar to S. cerevisiae GCN2 (YDR283C) eukaryotic initiation factor 2 alpha kinase Get druggable targets OG5_129525 All targets in OG5_129525
Loa Loa (eye worm) PEK/HRI protein kinase Get druggable targets OG5_130490 All targets in OG5_130490
Schistosoma japonicum ko:K08860 eukaryotic translation initiation factor 2-alpha kinase, putative Get druggable targets OG5_133221 All targets in OG5_133221
Entamoeba histolytica protein kinase domain containing protein Get druggable targets OG5_130490 All targets in OG5_130490
Trichomonas vaginalis STE family protein kinase Get druggable targets OG5_129525 All targets in OG5_129525
Echinococcus multilocularis raf serine:threonine protein kinase Get druggable targets OG5_130459 All targets in OG5_130459
Trypanosoma brucei protein kinase, putative Get druggable targets OG5_130490 All targets in OG5_130490
Leishmania mexicana protein kinase, putative Get druggable targets OG5_130490 All targets in OG5_130490
Schistosoma mansoni protein kinase Get druggable targets OG5_129525 All targets in OG5_129525
Echinococcus granulosus eukaryotic translation initiation factor 2 alpha Get druggable targets OG5_129525 All targets in OG5_129525
Schistosoma japonicum ko:K08860 eukaryotic translation initiation factor 2-alpha kinase, putative Get druggable targets OG5_129525 All targets in OG5_129525
Leishmania infantum protein kinase, putative Get druggable targets OG5_130490 All targets in OG5_130490
By sequence similarity to non orthologous known druggable targets
No druggable targets predicted by sequence similarity
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Leishmania major protein kinase, putative 0.01 0.3579 0.5
Loa Loa (eye worm) TKL/RAF/RAF protein kinase 0.0148 0.5489 0.5517
Loa Loa (eye worm) PEK/HRI protein kinase 0.01 0.3579 0.3597
Entamoeba histolytica protein kinase domain containing protein 0.01 0.3579 0.5
Brugia malayi hypothetical protein 0.01 0.3579 0.3714
Trypanosoma brucei eukaryotic translation initiation factor 2-alpha kinase 1, putative 0.01 0.3579 0.5
Schistosoma mansoni serine/threonine protein kinase 0.0262 1 1
Echinococcus granulosus eukaryotic translation initiation factor 2 alpha 0.0039 0.1142 0.1142
Brugia malayi Protein kinase domain containing protein 0.0229 0.8687 0.9015
Schistosoma mansoni protein kinase 0.0229 0.8687 0.8687
Brugia malayi Raf kinase 0.0253 0.9637 1
Trypanosoma brucei protein kinase, putative 0.01 0.3579 0.5
Echinococcus multilocularis raf serine:threonine protein kinase 0.0262 1 1
Trichomonas vaginalis STE family protein kinase 0.0038 0.1109 0.5
Loa Loa (eye worm) raf kinase 0.026 0.9949 1
Echinococcus multilocularis eukaryotic translation initiation factor 2 alpha 0.0039 0.1142 0.1142
Brugia malayi RWD domain containing protein 0.0039 0.1142 0.1185
Loa Loa (eye worm) PEK/PEK protein kinase 0.0229 0.8687 0.8731
Echinococcus granulosus eukaryotic translation initiation factor 2 alpha 0.01 0.3579 0.3579
Schistosoma mansoni protein kinase 0.0229 0.8687 0.8687
Echinococcus multilocularis eukaryotic translation initiation factor 2 alpha 0.01 0.3579 0.3579
Entamoeba histolytica protein kinase domain containing protein 0.01 0.3579 0.5
Loa Loa (eye worm) hypothetical protein 0.0038 0.1088 0.1094
Schistosoma mansoni protein kinase 0.004 0.116 0.116

Activities

Activity type Activity value Assay description Source Reference
EC50 (binding) = 520 nM Inhibition of PERK-mediated protein synthesis in human U2OS cells harboring thapsigargin-induced ER stress assessed as incorporation of L-azidohomoalanine into protein preincubated for 1 hr followed by thapsigargin induction measured over 30 mins by AlexaFluor 488 alkyne dye-based HCS assay ChEMBL. 25587754
IC50 (binding) Inhibition of doxycycline-inducible T-REx-PERK-FLAG (unknown origin) autophosphorylation tranfected in human HT1080 cells after 1 hr by sandwich ELISA ChEMBL. 25587754
IC50 (binding) Inhibition of GCN2 in amino acid starved human HT1080 cells assessed as inhibition of CHoP mRNA expression preincubated for 1 hr followed by 2 hrs incubation in DMEM lacking arginine, leucine, lysine by bDNA assay ChEMBL. 25587754
IC50 (binding) Inhibition of PERK in human HT1080 cells assessed as inhibition of thapsigargin-induced CHoP mRNA expression preincubated for 1 hr followed by thapsigargin-induction measured after 2 hrs by bDNA assay ChEMBL. 25587754
IC50 (binding) Inhibition of GCN2 phosphorylation in human U2OS cells preincubated for 1 hr followed by drug wash out and incubated for 2 hrs by MSD assay ChEMBL. 25587754
IC50 (binding) = 4 nM Inhibition of human N-terminal His-tagged PERK expressed in Escherichia coli using AviTag C-terminal, N-terminal His-tagged eIF2alpha (3 to 315) as substrate by LanthaScreen TR-FRET assay ChEMBL. 25587754
IC50 (binding) = 290 nM Inhibition of human C-terminal His-tagged GCN2 expressed in Escherichia coli using AviTag C-terminal, N-terminal His-tagged eIF2alpha (3 to 315) as substrate by LanthaScreen TR-FRET assay ChEMBL. 25587754
IC50 (binding) > 1000 nM Inhibition of recombinant BRAF V600E kinase domain mutant (unknown origin) ChEMBL. 25587754
IC50 (binding) > 10 uM Inhibition of HRI (unknown origin) ChEMBL. 25587754
IC50 (binding) > 50 uM Inhibition of IRE-1 (unknown origin) ChEMBL. 25587754
IC50 (binding) = 480 uM Inhibition of PKR (unknown origin) ChEMBL. 25587754

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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