Detailed information for compound 1980555

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 519.662 | Formula: C27H33N7O2S
  • H donors: 1 H acceptors: 6 LogP: 3.27 Rotable bonds: 6
    Rule of 5 violations (Lipinski): 2
  • SMILES: C[C@@H]1CC[C@H](CC1)n1c2nc(ncc2c2c1cncc2)Nc1ccc2c(n1)CCN(C2)CCS(=O)(=O)C
  • InChi: 1S/C27H33N7O2S/c1-18-3-6-20(7-4-18)34-24-16-28-11-9-21(24)22-15-29-27(32-26(22)34)31-25-8-5-19-17-33(12-10-23(19)30-25)13-14-37(2,35)36/h5,8-9,11,15-16,18,20H,3-4,6-7,10,12-14,17H2,1-2H3,(H,29,30,31,32)/t18-,20-
  • InChiKey: KYEMOBSMSCIMFC-KESTWPANSA-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 cyclin-dependent kinase 4 Starlite/ChEMBL No references
Homo sapiens fms-related tyrosine kinase 3 Starlite/ChEMBL No 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
Species Potential target Known druggable target Length Alignment span Identity
Trypanosoma brucei mitogen-activated protein kinase 5 cyclin-dependent kinase 4 303 aa 312 aa 29.8 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Entamoeba histolytica protein kinase domain containing protein 0.0002 0 0.5
Trypanosoma brucei STE/STE11 serine/threonine-protein kinase, putative 0.0002 0 0.5
Trypanosoma brucei protein kinase, putative 0.0002 0 0.5
Echinococcus multilocularis Immunoglobulin 0.0019 0.9064 1
Echinococcus granulosus twitchin 0.0019 0.937 1
Echinococcus granulosus defective proboscis extension response 0.0019 0.9064 0.9673
Loa Loa (eye worm) TK/KIN16 protein kinase 0.002 1 1
Toxoplasma gondii calcium dependent protein kinase CDPK8 0.0002 0 0.5
Trypanosoma cruzi STE/STE11 serine/threonine-protein kinase, putative 0.0002 0 0.5
Schistosoma mansoni defective proboscis extension response (dpr)-related 0.0019 0.9064 1
Echinococcus multilocularis basement membrane specific heparan sulfate 0.0019 0.9064 1
Schistosoma mansoni Neurotrimin precursor (hNT) 0.0019 0.9064 1
Echinococcus multilocularis roundabout 2 0.0019 0.9064 1
Echinococcus granulosus roundabout 2 0.0019 0.9064 0.9673
Schistosoma mansoni cell adhesion molecule 0.0019 0.9064 1
Schistosoma mansoni vesicular amine transporter 0.0019 0.9064 1
Echinococcus granulosus Immunoglobulin 0.0019 0.9064 0.9673
Trypanosoma cruzi STE/STE11 serine/threonine-protein kinase, putative 0.0002 0 0.5
Leishmania major protein kinase, putative 0.0002 0 0.5
Echinococcus granulosus neurotracting:lsamp:neurotrimin:obcam 0.0019 0.9064 0.9673
Schistosoma mansoni nephrin 0.0019 0.9064 1
Echinococcus multilocularis Immunoglobulin 0.0019 0.9064 1
Echinococcus granulosus neuroglian 0.0019 0.9064 0.9673
Echinococcus multilocularis neuroglian 0.0019 0.9064 1
Plasmodium falciparum protein kinase, putative 0.0002 0 0.5

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 2.4 nM BindingDB_Patents: Kinase Assay. The CDK4 and CDK1 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a filtration kinase assay. The compounds, kinase and substrate diluted in the kinase buffer (20 mM Tris, pH7.4, 50 mM NaCl, 1 mM DTT, 0.1% BSA) were sequentially added to a 96-well Multiscreen HTS filtration plate (Millipore). The final 100 µL reaction mixture in each well contained 0.3 µg of CDK4/Cyclin D1 or CDK1/Cyclin B (Cell Signaling Technology), 1 µg of Rb fragment (aa773-928, Millipore) for the CDK4 assay or 5 µg of histone H1 for the CDK1 assay and 1 µCi of [33P]-ATP. The mixture was incubated at room temperature for 1 hour. The proteins in the reaction were then precipitated and washed with cold TCA solution using an aspiration/filtration vacuum system. The plates were dried at room temperature, and the retained radioactivity was measured by scintillation counting. ChEMBL. No reference
IC50 (binding) = 2.4 nM BindingDB_Patents: Kinase Assay. The CDK4 and CDK1 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a filtration kinase assay. The compounds, kinase and substrate diluted in the kinase buffer (20 mM Tris, pH7.4, 50 mM NaCl, 1 mM DTT, 0.1% BSA) were sequentially added to a 96-well Multiscreen HTS filtration plate (Millipore). The final 100 µL reaction mixture in each well contained 0.3 µg of CDK4/Cyclin D1 or CDK1/Cyclin B (Cell Signaling Technology), 1 µg of Rb fragment (aa773-928, Millipore) for the CDK4 assay or 5 µg of histone H1 for the CDK1 assay and 1 µCi of [33P]-ATP. The mixture was incubated at room temperature for 1 hour. The proteins in the reaction were then precipitated and washed with cold TCA solution using an aspiration/filtration vacuum system. The plates were dried at room temperature, and the retained radioactivity was measured by scintillation counting. ChEMBL. No reference
IC50 (binding) = 36.1 nM BindingDB_Patents: Kinase Assay. The FLT3 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a HTRF kinase assay. The FLT3 enzyme (GST-FLT3 fusion) was purchased from Carna Biosciences. An ULight-labeled synthetic peptide derived from human Janus kinase 1 (aa1015-1027, ULight-JAK1, PerkinElmer) was utilized as the phosphoacceptor substrate. The assay was conducted in a 384-well white OptiPlate (PerkinElmer). The 20 µL reaction mixture contained 50 nM ULight-JAK1, 116 µM ATP, 0.0385 ng/µL FLT3 and dilutions of test compounds in the kinase buffer (50 mM Hepes, pH 7.6, 1 mM EGTA, 10 mM MgCl2, 2 mM DTT, and 0.005% Tween 20). The reaction was allowed to proceed for 1 hour at room temperature and was stopped by adding 20 µL of 10 mM EDTA, 2 nM LANCE Eu-W1024 anti-phospho-tyrosine antibody in LANCE detection buffer (PerkinElmer). The plates were incubated at room temperature for 2 hours after addition of detection reagents and then read on an Envision multimode reader (PerkinElmer). ChEMBL. No reference
IC50 (binding) = 36.1 nM BindingDB_Patents: Kinase Assay. The FLT3 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a HTRF kinase assay. The FLT3 enzyme (GST-FLT3 fusion) was purchased from Carna Biosciences. An ULight-labeled synthetic peptide derived from human Janus kinase 1 (aa1015-1027, ULight-JAK1, PerkinElmer) was utilized as the phosphoacceptor substrate. The assay was conducted in a 384-well white OptiPlate (PerkinElmer). The 20 µL reaction mixture contained 50 nM ULight-JAK1, 116 µM ATP, 0.0385 ng/µL FLT3 and dilutions of test compounds in the kinase buffer (50 mM Hepes, pH 7.6, 1 mM EGTA, 10 mM MgCl2, 2 mM DTT, and 0.005% Tween 20). The reaction was allowed to proceed for 1 hour at room temperature and was stopped by adding 20 µL of 10 mM EDTA, 2 nM LANCE Eu-W1024 anti-phospho-tyrosine antibody in LANCE detection buffer (PerkinElmer). The plates were incubated at room temperature for 2 hours after addition of detection reagents and then read on an Envision multimode reader (PerkinElmer). 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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