Detailed information for compound 2128148

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 376.154 | Formula: C21H20N4O3
  • H donors: 2 H acceptors: 3 LogP: 2.82 Rotable bonds: 5
    Rule of 5 violations (Lipinski): 0
  • SMILES: O=C(c1noc(c1)Cc1ccccc1)N[C@H]1CNc2c(N(C1=O)C)cccc2
  • InChi: InChI=1S/C21H20N4O3/c1-25-19-10-6-5-9-16(19)22-13-18(21(25)27)23-20(26)17-12-15(28-24-17)11-14-7-3-2-4-8-14/h2-10,12,18,22H,11,13H2,1H3,(H,23,26)/t18-/m0/s1
  • InChiKey: FILOHPAPJRJFDF-SFHVURJKSA-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
Mus musculus receptor (TNFRSF)-interacting serine-threonine kinase 1 References
Homo sapiens receptor (TNFRSF)-interacting serine-threonine kinase 1 References

Predicted pathogen targets for this compound

By orthology
No druggable targets predicted by orthology data
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
Schistosoma mansoni hypothetical protein 0.0052 0.5 0.5
Echinococcus granulosus death domain containing protein 0.0052 0.5 0.5
Schistosoma mansoni netrin receptor unc5 0.0052 0.5 0.5
Echinococcus granulosus ankyrin repeat and death domain containing protein 0.0052 0.5 0.5
Onchocerca volvulus Netrin receptor homolog 0.0052 0.5 0.5
Brugia malayi Immunoglobulin I-set domain containing protein 0.0052 0.5 0.5
Loa Loa (eye worm) hypothetical protein 0.0052 0.5 0.5
Echinococcus multilocularis netrin receptor unc 5 0.0052 0.5 0.5
Echinococcus multilocularis ankyrin repeat and death domain containing protein 0.0052 0.5 0.5
Echinococcus granulosus Ankyrin 0.0052 0.5 0.5
Brugia malayi Death domain containing protein 0.0052 0.5 0.5
Schistosoma mansoni ankyrin 23/unc44 0.0052 0.5 0.5
Echinococcus multilocularis Ankyrin 0.0052 0.5 0.5
Loa Loa (eye worm) immunoglobulin I-set domain-containing protein 0.0052 0.5 0.5
Loa Loa (eye worm) hypothetical protein 0.0052 0.5 0.5
Brugia malayi Protein kinase domain containing protein 0.0052 0.5 0.5
Echinococcus granulosus netrin receptor unc 5 0.0052 0.5 0.5
Schistosoma mansoni retinoblastoma-binding protein 4 (rbbp4) 0.0052 0.5 0.5

Activities

Activity type Activity value Assay description Source Reference
Activity (functional) = 8 % Protection against body temperature loss in mouse model of TNF/zVAD-induced TNF-driven systemic inflammatory response syndrome model at 3 mg/kg, po administered 15 mins prior to TNF/zVAD.fmk challenge measured after 3 hrs ChEMBL. 26854747
Activity (functional) = 24 % Protection against body temperature loss in mouse model of TNF/zVAD-induced TNF-driven systemic inflammatory response syndrome model at 10 mg/kg, po administered 15 mins prior to TNF/zVAD.fmk challenge measured after 3 hrs ChEMBL. 26854747
Activity (functional) = 82 % Protection against body temperature loss in mouse model of TNF/zVAD-induced TNF-driven systemic inflammatory response syndrome model at 50 mg/kg, po administered 15 mins prior to TNF/zVAD.fmk challenge measured after 8 hrs ChEMBL. 26854747
AUC (ADMET) = 0.31 ug.hr/ml AUC(0 to infinity) in mouse at 1 mg/kg, iv ChEMBL. 26854747
AUC (ADMET) = 0.46 ug.hr/ml AUC(0 to infinity) in mouse at 2 mg/kg, po ChEMBL. 26854747
AUC (ADMET) = 2 ug.hr/ml AUC(0 to infinity) in mouse at 30 mg/kg, po ChEMBL. 26854747
IC50 (functional) = 640 ng/ml Protection against body temperature loss in mouse model of TNF/zVAD-induced TNF-driven systemic inflammatory response syndrome model at 3 to 50 mg/kg, po administered 15 mins prior to TNF/zVAD.fmk challenge measured after 3 to 8 hrs ChEMBL. 26854747
IC50 (binding) = 0.79 nM Inhibition of human RIP1 (1 to 375 residues) after 4 hrs by ADP-Glo reagent based assay ChEMBL. 26854747
IC50 (binding) = 1 uM Binding affinity to mouse RIP1 (1 to 378 residues) preincubated for 10 mins measured after 20 mins by fluorescence polarization assay ChEMBL. 26854747
IC50 (binding) = 3.2 uM Inhibition of mouse RIP1 in mouse L929 cells assessed as inhibition of TNF/zVAD.fmk induced necroptosis by Cell titer-Glo luminescence assay ChEMBL. 26854747
K (binding) = 0.35 /uM/s Binding affinity to human RIP1 (1 to 375 residues) by stopped flow kinetic study ChEMBL. 26854747
T1/2 (ADMET) = 1.5 hr Half life in mouse at 30 mg/kg, po ChEMBL. 26854747
T1/2 (binding) > 50 min Binding affinity to human RIP1 (1 to 375 residues) assessed as half life preincubated for 10 mins measured after 20 mins by fluorescence polarization assay ChEMBL. 26854747

Phenotypes

Whole-cell/tissue/organism interactions

Species name Source Reference Is orphan
Mus musculus 26854747

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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