Species | Target name | Source | Bibliographic reference |
---|---|---|---|
Mus musculus | mitogen-activated protein kinase 3 | No references | |
Mus musculus | mitogen-activated protein kinase 1 | No references |
Species | Potential target | Known druggable target | Length | Alignment span | Identity |
---|---|---|---|---|---|
Trypanosoma brucei | mitogen-activated protein kinase 5 | mitogen-activated protein kinase 1 | 358 aa | 361 aa | 33.2 % |
Trypanosoma cruzi | casein kinase II, alpha chain, putative | mitogen-activated protein kinase 3 | 380 aa | 332 aa | 31.9 % |
Species | Potential target | Raw | Global | Species |
---|---|---|---|---|
Trichomonas vaginalis | CMGC family protein kinase | 0.0123 | 0.5 | 0.5 |
Schistosoma mansoni | serine/threonine protein kinase | 0.0123 | 0.5 | 0.5 |
Echinococcus multilocularis | mitogen activated protein kinase | 0.0123 | 0.5 | 0.5 |
Trypanosoma brucei | protein kinase, putative | 0.0123 | 0.5 | 0.5 |
Trypanosoma cruzi | mitogen activated protein kinase 4, putative | 0.0123 | 0.5 | 0.5 |
Trichomonas vaginalis | CMGC family protein kinase | 0.0123 | 0.5 | 0.5 |
Trichomonas vaginalis | CMGC family protein kinase | 0.0123 | 0.5 | 0.5 |
Trichomonas vaginalis | CMGC family protein kinase | 0.0123 | 0.5 | 0.5 |
Echinococcus granulosus | mitogen activated protein kinase | 0.0123 | 0.5 | 0.5 |
Echinococcus granulosus | mitogen activated protein kinase 3 | 0.0123 | 0.5 | 0.5 |
Leishmania major | mitogen activated protein kinase 4, putative;with=GeneDB:LmxM19.1440 | 0.0123 | 0.5 | 0.5 |
Leishmania major | mitogen activated protein kinase, putative,map kinase, putative | 0.0123 | 0.5 | 0.5 |
Trypanosoma cruzi | mitogen-activated protein kinase 11, putative | 0.0123 | 0.5 | 0.5 |
Trypanosoma cruzi | mitogen activated protein kinase 2, putative | 0.0123 | 0.5 | 0.5 |
Loa Loa (eye worm) | CMGC/MAPK/ERK1 protein kinase | 0.0123 | 0.5 | 0.5 |
Toxoplasma gondii | CMGC kinase, MAPK family (ERK) MAPK-1 | 0.0123 | 0.5 | 0.5 |
Echinococcus multilocularis | mitogen activated protein kinase 3 | 0.0123 | 0.5 | 0.5 |
Giardia lamblia | Kinase, CMGC MAPK | 0.0123 | 0.5 | 0.5 |
Trypanosoma brucei | mitogen activated protein kinase 4, putative | 0.0123 | 0.5 | 0.5 |
Trypanosoma cruzi | mitogen-activated protein kinase 11, putative | 0.0123 | 0.5 | 0.5 |
Activity type | Activity value | Assay description | Source | Reference |
---|---|---|---|---|
IC50 (binding) | = 263.67 nM | BindingDB_Patents: IMAP Assay. Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 µl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 µl of kinase buffer containing 1 µM ERK2 IMAP substrate peptide (0.9 µM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 µM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 µl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay. | ChEMBL. | No reference |
IC50 (binding) | = 263.67 nM | BindingDB_Patents: IMAP Assay. Condition 1: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 µl of 25× compound was added to 140 of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 µl of kinase buffer containing 1 µM ERK2 IMAP substrate peptide (0.9 µM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 µM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 µl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay. | ChEMBL. | No reference |
Kd (binding) | = 0.83 nM | BindingDB_Patents: Temperature Dependence Fluorescence Assay (TdF). The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT). | ChEMBL. | No reference |
Kd (binding) | = 0.83 nM | BindingDB_Patents: Temperature Dependence Fluorescence Assay (TdF). The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT). | ChEMBL. | No reference |
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.