Detailed information for compound 1975023
Basic information
Technical information
- Name: Unnamed compound
- MW: 411.499 | Formula: C25H25N5O
-
H donors: 2
H acceptors: 3
LogP: 3.51
Rotable bonds: 6
Rule of 5 violations (Lipinski): 1 - SMILES: O=C(c1ccc2c(c1)c(n[nH]2)c1ccncc1)NC1CCCN(C1)Cc1ccccc1
- InChi: 1S/C25H25N5O/c31-25(27-21-7-4-14-30(17-21)16-18-5-2-1-3-6-18)20-8-9-23-22(15-20)24(29-28-23)19-10-12-26-13-11-19/h1-3,5-6,8-13,15,21H,4,7,14,16-17H2,(H,27,31)(H,28,29)
- InChiKey: RJCLUDCGUNLXRQ-UHFFFAOYSA-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 |
|---|---|---|---|
| Mus musculus | mitogen-activated protein kinase 1 | Starlite/ChEMBL | No references |
| Mus musculus | mitogen-activated protein kinase 3 | Starlite/ChEMBL | No references |
Predicted pathogen targets for this compound
By orthology
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 | 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 % |
Obtained from network model
Ranking Plot
Putative Targets List
| Species | Potential target | Raw | Global | Species |
|---|---|---|---|---|
| Trichomonas vaginalis | CMGC family protein kinase | 0.0123 | 0.5 | 0.5 |
| Echinococcus granulosus | mitogen activated protein kinase | 0.0123 | 0.5 | 0.5 |
| Trichomonas vaginalis | CMGC family protein kinase | 0.0123 | 0.5 | 0.5 |
| Leishmania major | mitogen activated protein kinase 4, putative;with=GeneDB:LmxM19.1440 | 0.0123 | 0.5 | 0.5 |
| Echinococcus granulosus | mitogen activated protein kinase 3 | 0.0123 | 0.5 | 0.5 |
| Echinococcus multilocularis | mitogen activated protein kinase | 0.0123 | 0.5 | 0.5 |
| Schistosoma mansoni | serine/threonine 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 |
| Trypanosoma cruzi | mitogen activated protein kinase 4, putative | 0.0123 | 0.5 | 0.5 |
| Trypanosoma brucei | protein kinase, putative | 0.0123 | 0.5 | 0.5 |
| Giardia lamblia | Kinase, CMGC MAPK | 0.0123 | 0.5 | 0.5 |
| Echinococcus multilocularis | mitogen activated protein kinase 3 | 0.0123 | 0.5 | 0.5 |
| Toxoplasma gondii | CMGC kinase, MAPK family (ERK) MAPK-1 | 0.0123 | 0.5 | 0.5 |
| Trypanosoma cruzi | mitogen-activated protein kinase 11, putative | 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 2, putative | 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 |
| Loa Loa (eye worm) | CMGC/MAPK/ERK1 protein kinase | 0.0123 | 0.5 | 0.5 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| IC50 (binding) | = 16.6 nM | BindingDB_Patents: Coupled ERK2 (cERK) Assay. Activity of compounds against inactive ERK2 was tested in a coupled MEK1/ERK2 IMAP assay as follows: Compounds were diluted to 25x final test concentration in 100% DMSO. 14 ul of kinase buffer (10 mM Tris.HCl pH 7.2, 10 mM MgCl2, 0.01% Tween-20, 1 mM DTT) containing 0.4 ng unphosphorylated Mouse ERK2 protein was added to each well of a black 384-well assay plate. 1 ul of 25x compound was added to each well and incubated at room temperature for 30 minutes to allow an opportunity for the compound to bind to the inactive enzyme. DMSO concentration during initial incubation is 6.7%. ERK2 activity was determined to be insensitive to DMSO concentrations up to 20%. ERK2 was then activated and it's kinase activity measured by the addition of 10 ul kinase buffer with the following components (final concentration per reaction): 2 ng active (phosphorylated) human MEK1 protein and 4 uM (total) ERK2 IMAP substrate peptides. | ChEMBL. | No reference |
| IC50 (binding) | = 16.6 nM | BindingDB_Patents: Coupled ERK2 (cERK) Assay. Activity of compounds against inactive ERK2 was tested in a coupled MEK1/ERK2 IMAP assay as follows: Compounds were diluted to 25x final test concentration in 100% DMSO. 14 ul of kinase buffer (10 mM Tris.HCl pH 7.2, 10 mM MgCl2, 0.01% Tween-20, 1 mM DTT) containing 0.4 ng unphosphorylated Mouse ERK2 protein was added to each well of a black 384-well assay plate. 1 ul of 25x compound was added to each well and incubated at room temperature for 30 minutes to allow an opportunity for the compound to bind to the inactive enzyme. DMSO concentration during initial incubation is 6.7%. ERK2 activity was determined to be insensitive to DMSO concentrations up to 20%. ERK2 was then activated and it's kinase activity measured by the addition of 10 ul kinase buffer with the following components (final concentration per reaction): 2 ng active (phosphorylated) human MEK1 protein and 4 uM (total) ERK2 IMAP substrate peptides. | ChEMBL. | No reference |
| IC50 (binding) | = 32.5 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) | = 32.5 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) | = 0.6 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) | = 0.6 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 |
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.
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
- ChEMBL: CHEMBL3654460
Bibliographic References
No literature references available for this target.
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