Detailed information for compound 1964060

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 362.425 | Formula: C21H22N4O2
  • H donors: 1 H acceptors: 3 LogP: 4.15 Rotable bonds: 4
    Rule of 5 violations (Lipinski): 1
  • SMILES: O=C1OCC(N1c1ccnc(n1)N[C@H](c1ccc2c(c1)cccc2)C)(C)C
  • InChi: 1S/C21H22N4O2/c1-14(16-9-8-15-6-4-5-7-17(15)12-16)23-19-22-11-10-18(24-19)25-20(26)27-13-21(25,2)3/h4-12,14H,13H2,1-3H3,(H,22,23,24)/t14-/m0/s1
  • InChiKey: ZOELTMFQLAGRRR-AWEZNQCLSA-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 isocitrate dehydrogenase 1 (NADP+), soluble Starlite/ChEMBL No references

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Trypanosoma brucei gambiense isocitrate dehydrogenase [NADP], mitochondrial precursor, putative Get druggable targets OG5_127057 All targets in OG5_127057
Babesia bovis isocitrate dehydrogenase, NADP-dependent family protein Get druggable targets OG5_127057 All targets in OG5_127057
Leishmania mexicana isocitrate dehydrogenase [NADP], mitochondrial precursor, putative Get druggable targets OG5_127057 All targets in OG5_127057
Trypanosoma brucei gambiense isocitrate dehydrogenase, putative Get druggable targets OG5_127057 All targets in OG5_127057
Brugia malayi isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Echinococcus granulosus NADP dependent isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Trypanosoma congolense isocitrate dehydrogenase, putative Get druggable targets OG5_127057 All targets in OG5_127057
Neospora caninum hypothetical protein Get druggable targets OG5_127057 All targets in OG5_127057
Trypanosoma cruzi isocitrate dehydrogenase, putative Get druggable targets OG5_127057 All targets in OG5_127057
Echinococcus multilocularis NADP dependent isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Leishmania donovani isocitrate dehydrogenase [NADP], mitochondrial precursor, putative Get druggable targets OG5_127057 All targets in OG5_127057
Trypanosoma brucei isocitrate dehydrogenase, putative Get druggable targets OG5_127057 All targets in OG5_127057
Plasmodium yoelii isocitrate dehydrogenase, NADP-dependent Get druggable targets OG5_127057 All targets in OG5_127057
Leishmania major isocitrate dehydrogenase [NADP], mitochondrial precursor, putative Get druggable targets OG5_127057 All targets in OG5_127057
Trypanosoma brucei isocitrate dehydrogenase [NADP], mitochondrial precursor, putative Get druggable targets OG5_127057 All targets in OG5_127057
Candida albicans cytosolic NADP-specific isocitrate dehydrogenase. Get druggable targets OG5_127057 All targets in OG5_127057
Echinococcus multilocularis NADP dependent isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Trypanosoma cruzi isocitrate dehydrogenase [NADP], mitochondrial precursor, putative Get druggable targets OG5_127057 All targets in OG5_127057
Toxoplasma gondii isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Schistosoma mansoni NADP-specific isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Trypanosoma congolense isocitrate dehydrogenase, putative Get druggable targets OG5_127057 All targets in OG5_127057
Plasmodium knowlesi isocitrate dehydrogenase [NADP], mitochondrial, putative Get druggable targets OG5_127057 All targets in OG5_127057
Plasmodium berghei isocitrate dehydrogenase [NADP], mitochondrial, putative Get druggable targets OG5_127057 All targets in OG5_127057
Loa Loa (eye worm) isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Leishmania infantum isocitrate dehydrogenase [NADP], mitochondrial precursor, putative Get druggable targets OG5_127057 All targets in OG5_127057
Theileria parva isocitrate dehydrogenase (NADP+), putative Get druggable targets OG5_127057 All targets in OG5_127057
Candida albicans Mitochondrial NADP-specific isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Schistosoma japonicum ko:K00031 isocitrate dehydrogenase [EC1.1.1.42], putative Get druggable targets OG5_127057 All targets in OG5_127057
Leishmania braziliensis isocitrate dehydrogenase [NADP], mitochondrial precursor, putative Get druggable targets OG5_127057 All targets in OG5_127057
Echinococcus multilocularis isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Brugia malayi Isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Echinococcus multilocularis NADP dependent isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Candida albicans C terminus of cytosolic NADP-specific isocitrate dehydrogenase. Get druggable targets OG5_127057 All targets in OG5_127057
Candida albicans Mitochondrial NADP-specific isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Toxoplasma gondii isocitrate dehydrogenase Get druggable targets OG5_127057 All targets in OG5_127057
Neospora caninum Isocitrate dehydrogenase-like protein, related Get druggable targets OG5_127057 All targets in OG5_127057
Plasmodium falciparum isocitrate dehydrogenase [NADP], mitochondrial Get druggable targets OG5_127057 All targets in OG5_127057
Mycobacterium tuberculosis Probable isocitrate dehydrogenase [NADP] Icd1 (oxalosuccinate decarboxylase) (IDH) (NADP+-specific ICDH) (IDP) Get druggable targets OG5_127057 All targets in OG5_127057
Candida albicans N terminus of cytosolic NADP-specific isocitrate dehydrogenase. Get druggable targets OG5_127057 All targets in OG5_127057
Plasmodium yoelii isocitrate dehydrogenase, NADP-dependent, putative Get druggable targets OG5_127057 All targets in OG5_127057
Echinococcus multilocularis isocitrate dehydrogenase 2 (NADP+) Get druggable targets OG5_127057 All targets in OG5_127057
Plasmodium vivax isocitrate dehydrogenase [NADP], mitochondrial, putative Get druggable targets OG5_127057 All targets in OG5_127057
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 atypical protein kinase C 0.0091 0.1928 0.3337
Echinococcus granulosus unc 13 munc13 0.0045 0.0174 0.0302
Echinococcus granulosus protein kinase c epsilon type 0.0179 0.5249 0.9085
Loa Loa (eye worm) hypothetical protein 0.0254 0.8072 0.8072
Echinococcus multilocularis ribosomal protein S6 kinase alpha 3 0.0051 0.0421 0.0729
Schistosoma mansoni serine/threonine protein kinase 0.0051 0.0421 0.0729
Loa Loa (eye worm) AGC/RSK/MSK protein kinase 0.0051 0.0421 0.0421
Echinococcus granulosus ribosomal protein s6 kinase beta 1 0.0051 0.0421 0.0729
Loa Loa (eye worm) hypothetical protein 0.0045 0.0174 0.0174
Brugia malayi protein kinase C3,putative 0.0041 0.0042 0.0079
Echinococcus multilocularis unc 13 (munc13) 0.0045 0.0174 0.0302
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Schistosoma mansoni serine/threonine kinase 0.0051 0.0421 0.0729
Echinococcus granulosus Ribosomal protein S6 kinase beta 2 0.0051 0.0421 0.0729
Loa Loa (eye worm) AGC/PKC/ALPHA protein kinase 0.0103 0.2384 0.2384
Loa Loa (eye worm) AGC/PKC/IOTA protein kinase 0.0041 0.0042 0.0042
Brugia malayi C1-like domain containing protein 0.0041 0.0042 0.0079
Echinococcus multilocularis ribosomal protein s6 kinase beta 1 0.0051 0.0421 0.0729
Echinococcus granulosus NDR protein kinase 0.0051 0.0421 0.0729
Echinococcus granulosus ribosomal protein S6 kinase alpha 3 0.0051 0.0421 0.0729
Echinococcus granulosus RNA directed DNA polymerase 0.0098 0.2168 0.3752
Schistosoma mansoni serine/threonine protein kinase 0.0041 0.0042 0.0072
Echinococcus multilocularis Protein kinase C, brain isozyme 0.0193 0.5778 1
Loa Loa (eye worm) AGC/RSK/RSK protein kinase 0.0051 0.0421 0.0421
Schistosoma mansoni unc-13 (munc13) 0.0045 0.0174 0.0302
Brugia malayi Protein kinase domain containing protein 0.0051 0.0421 0.0802
Loa Loa (eye worm) hypothetical protein 0.0098 0.2168 0.2168
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Schistosoma mansoni protein kinase C mu 0.0041 0.0042 0.0072
Loa Loa (eye worm) hypothetical protein 0.0138 0.3686 0.3686
Echinococcus multilocularis C2 calcium dependent membrane targeting 0.0045 0.0174 0.0302
Loa Loa (eye worm) hypothetical protein 0.0294 0.9579 0.9579
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Brugia malayi RasGEF domain containing protein 0.0079 0.1488 0.2834
Brugia malayi Protein kinase domain containing protein 0.0051 0.0421 0.0802
Echinococcus granulosus biogenic amine 5HT receptor 0.0138 0.3686 0.6379
Entamoeba histolytica protein kinase, putative 0.0051 0.0421 0.2505
Loa Loa (eye worm) AGC/NDR protein kinase 0.0051 0.0421 0.0421
Echinococcus multilocularis Ribosomal protein S6 kinase beta 2 0.0051 0.0421 0.0729
Echinococcus granulosus serine:threonine protein kinase N2 0.0085 0.1681 0.291
Loa Loa (eye worm) CAMK/PKD protein kinase 0.0041 0.0042 0.0042
Schistosoma mansoni serine/threonine protein kinase 0.0179 0.5249 0.9085
Loa Loa (eye worm) hypothetical protein 0.0254 0.8072 0.8072
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Loa Loa (eye worm) AGC/DMPK/GEK protein kinase 0.0051 0.0421 0.0421
Echinococcus multilocularis serine:threonine protein kinase N2 0.0051 0.0421 0.0729
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Echinococcus granulosus C2 calcium dependent membrane targeting 0.0045 0.0174 0.0302
Echinococcus granulosus Protein kinase C brain isozyme 0.0193 0.5778 1
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Schistosoma mansoni protein kinase C 0.0045 0.0174 0.0302
Echinococcus multilocularis serine:threonine protein kinase N2 0.0135 0.3568 0.6175
Loa Loa (eye worm) AGC/PKN protein kinase 0.0051 0.0421 0.0421
Loa Loa (eye worm) hypothetical protein 0.0138 0.3675 0.3675
Echinococcus multilocularis RNA directed DNA polymerase 0.0098 0.2168 0.3752
Echinococcus multilocularis protein kinase c epsilon type 0.0179 0.5249 0.9085
Echinococcus multilocularis serotonin receptor 0.0138 0.3686 0.6379
Schistosoma mansoni serine/threonine protein kinase 0.0193 0.5778 1
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Brugia malayi Protein kinase c protein 2 0.0143 0.3891 0.7413
Entamoeba histolytica protein kinase, putative 0.0051 0.0421 0.2505
Echinococcus multilocularis protein kinase c iota type 0.0091 0.1928 0.3337
Schistosoma mansoni serine/threonine protein kinase 0.0041 0.0042 0.0072
Brugia malayi Phorbol esters/diacylglycerol binding domain 0.0041 0.0042 0.0079
Loa Loa (eye worm) AGC/AKT protein kinase 0.0051 0.0421 0.0421
Echinococcus granulosus Serine/threonine-protein kinase Genghis Khan 0.0041 0.0042 0.0072
Brugia malayi Hr1 repeat family protein 0.0051 0.0421 0.0802
Echinococcus multilocularis serine:threonine protein kinase MRCK beta 0.0041 0.0042 0.0072
Echinococcus multilocularis serine threonine protein kinase 0.0153 0.4271 0.7391
Entamoeba histolytica protein kinase, putative 0.0051 0.0421 0.2505
Echinococcus granulosus serine:threonine protein kinase N2 0.0051 0.0421 0.0729
Schistosoma mansoni unc-13 (munc13) 0.0047 0.0262 0.0453
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Brugia malayi p70 ribosomal S6 kinase beta 0.0051 0.0421 0.0802
Echinococcus multilocularis telomerase reverse transcriptase subunit 0.0098 0.2168 0.3752
Toxoplasma gondii AGC kinase 0.0051 0.0421 1
Loa Loa (eye worm) hypothetical protein 0.0138 0.3686 0.3686
Entamoeba histolytica PH domain containing protein kinase, putative 0.0085 0.1681 1
Loa Loa (eye worm) hypothetical protein 0.0254 0.8072 0.8072
Brugia malayi protein kinase C II. 0.0179 0.5249 1
Echinococcus granulosus protein kinase c iota type 0.0091 0.1928 0.3337
Schistosoma mansoni serine/threonine protein kinase 0.0051 0.0421 0.0729
Schistosoma mansoni biogenic amine (5HT) receptor 0.0138 0.3686 0.6379
Loa Loa (eye worm) RasGEF domain-containing protein 0.0119 0.2995 0.2995
Entamoeba histolytica protein kinase, putative 0.0051 0.0421 0.2505
Trypanosoma brucei rac serine-threonine kinase, putative 0.0051 0.0421 0.5
Brugia malayi Protein kinase domain containing protein 0.0041 0.0042 0.0079
Loa Loa (eye worm) AGC/RSK/P70 protein kinase 0.0051 0.0421 0.0421
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Schistosoma mansoni serine/threonine protein kinase 0.0051 0.0421 0.0729
Brugia malayi Protein kinase domain containing protein 0.0051 0.0421 0.0802
Trichomonas vaginalis AGC family protein kinase 0.0051 0.0421 1
Schistosoma mansoni serine/threonine protein kinase 0.0193 0.5778 1
Onchocerca volvulus 0.0254 0.8072 1
Schistosoma mansoni serine/threonine protein kinase 0.0051 0.0421 0.0729
Echinococcus multilocularis serine:threonine protein kinase 38 0.0051 0.0421 0.0729
Echinococcus multilocularis serotonin receptor 0.0138 0.3686 0.6379
Onchocerca volvulus 0.0045 0.0174 0.0216
Echinococcus granulosus protein kinase C gamma type 0.0153 0.4271 0.7391
Loa Loa (eye worm) AGC/PKC/ETA protein kinase 0.0179 0.5249 0.5249

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 158 nM BindingDB_Patents: LC-MS Biochemical Assay. Mutant IDH1 R132H catalytic activity was monitored using the quantitative liquid chromatography/mass spectrometry (LC-MS) detection of 2-HG, a product of the NADPH-dependent alpha-KG reduction reaction.More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Costar, Cat. No. 781201) using a final reaction volume of 30 uL and the following assay buffer conditions: 50 mM HEPES pH 7.4, 10 mM MgCl2, 50 mM KCl, 1 mM DTT, 0.02% BSA, 5 uM NADPH and 100 uM alpha-KG.The final reaction mixture contained 3.3% DMSO and inhibitors with concentrations ranging 0.02-50 uM. The IDH1 enzyme was used at a final concentration of 0.25 nM. Following 45 minutes incubation, the reaction mixtures were quenched by the addition of 10 uL of 16% formic acid containing 800 nM of 5-carbon labeled 13C-2-HG). The protein was then precipitated by the addition of 2.5 volumes of acetonitrile followed by centrifugation (3000xg, 20 minutes). ChEMBL. No reference
IC50 (binding) = 158 nM BindingDB_Patents: LC-MS Biochemical Assay. Mutant IDH1 R132H catalytic activity was monitored using the quantitative liquid chromatography/mass spectrometry (LC-MS) detection of 2-HG, a product of the NADPH-dependent alpha-KG reduction reaction.More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Costar, Cat. No. 781201) using a final reaction volume of 30 uL and the following assay buffer conditions: 50 mM HEPES pH 7.4, 10 mM MgCl2, 50 mM KCl, 1 mM DTT, 0.02% BSA, 5 uM NADPH and 100 uM alpha-KG.The final reaction mixture contained 3.3% DMSO and inhibitors with concentrations ranging 0.02-50 uM. The IDH1 enzyme was used at a final concentration of 0.25 nM. Following 45 minutes incubation, the reaction mixtures were quenched by the addition of 10 uL of 16% formic acid containing 800 nM of 5-carbon labeled 13C-2-HG). The protein was then precipitated by the addition of 2.5 volumes of acetonitrile followed by centrifugation (3000xg, 20 minutes). ChEMBL. No reference
IC50 (binding) = 215 nM BindingDB_Patents: Fluorescence Biochemical Assay. The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and a-ketoglutarate (a-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (-)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 µL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 µM NADPH and 100 µM a-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 µM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM. ChEMBL. No reference
IC50 (binding) = 215 nM BindingDB_Patents: Fluorescence Biochemical Assay. The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and a-ketoglutarate (a-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (-)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 µL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 µM NADPH and 100 µM a-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 µM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM. 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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