Residence time and kinetic efficiency analysis of extracellular signal-regulated kinase 2 inhibitors
The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of vari...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Vanderpool, Darin [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2015transfer abstract |
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| Umfang: |
7 |
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| Übergeordnetes Werk: |
Enthalten in: Informing policy to protect coastal coral reefs: Insight from a global review of reducing agricultural pollution to coastal ecosystems - Kroon, Frederieke J. ELSEVIER, 2014, methods in the biological sciences, San Diego, Calif |
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| Übergeordnetes Werk: |
volume:473 ; year:2015 ; day:15 ; month:03 ; pages:46-52 ; extent:7 |
| Links: |
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| DOI / URN: |
10.1016/j.ab.2014.12.008 |
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| 520 | |a The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. | ||
| 520 | |a The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. | ||
| 650 | 7 | |a ERK2 |2 Elsevier | |
| 650 | 7 | |a Time-dependent inhibition |2 Elsevier | |
| 650 | 7 | |a Residence time |2 Elsevier | |
| 650 | 7 | |a Kinetic efficiency |2 Elsevier | |
| 650 | 7 | |a Off-rate |2 Elsevier | |
| 650 | 7 | |a Structure–kinetic relationship |2 Elsevier | |
| 700 | 1 | |a Grimshaw, Charles E. |4 oth | |
| 700 | 1 | |a Lawson, J. David |4 oth | |
| 700 | 1 | |a Ermolieff, Jacques |4 oth | |
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10.1016/j.ab.2014.12.008 doi GBVA2015019000030.pica (DE-627)ELV039904148 (ELSEVIER)S0003-2697(14)00568-5 DE-627 ger DE-627 rakwb eng 570 540 570 DE-600 540 DE-600 550 VZ 333.7 VZ 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Vanderpool, Darin verfasserin aut Residence time and kinetic efficiency analysis of extracellular signal-regulated kinase 2 inhibitors 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. ERK2 Elsevier Time-dependent inhibition Elsevier Residence time Elsevier Kinetic efficiency Elsevier Off-rate Elsevier Structure–kinetic relationship Elsevier Grimshaw, Charles E. oth Lawson, J. David oth Ermolieff, Jacques oth Enthalten in Elsevier Kroon, Frederieke J. ELSEVIER Informing policy to protect coastal coral reefs: Insight from a global review of reducing agricultural pollution to coastal ecosystems 2014 methods in the biological sciences San Diego, Calif (DE-627)ELV018040411 volume:473 year:2015 day:15 month:03 pages:46-52 extent:7 https://doi.org/10.1016/j.ab.2014.12.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA 44.40 Pharmazie Pharmazeutika VZ AR 473 2015 15 0315 46-52 7 045F 570 |
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10.1016/j.ab.2014.12.008 doi GBVA2015019000030.pica (DE-627)ELV039904148 (ELSEVIER)S0003-2697(14)00568-5 DE-627 ger DE-627 rakwb eng 570 540 570 DE-600 540 DE-600 550 VZ 333.7 VZ 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Vanderpool, Darin verfasserin aut Residence time and kinetic efficiency analysis of extracellular signal-regulated kinase 2 inhibitors 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. ERK2 Elsevier Time-dependent inhibition Elsevier Residence time Elsevier Kinetic efficiency Elsevier Off-rate Elsevier Structure–kinetic relationship Elsevier Grimshaw, Charles E. oth Lawson, J. David oth Ermolieff, Jacques oth Enthalten in Elsevier Kroon, Frederieke J. ELSEVIER Informing policy to protect coastal coral reefs: Insight from a global review of reducing agricultural pollution to coastal ecosystems 2014 methods in the biological sciences San Diego, Calif (DE-627)ELV018040411 volume:473 year:2015 day:15 month:03 pages:46-52 extent:7 https://doi.org/10.1016/j.ab.2014.12.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA 44.40 Pharmazie Pharmazeutika VZ AR 473 2015 15 0315 46-52 7 045F 570 |
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10.1016/j.ab.2014.12.008 doi GBVA2015019000030.pica (DE-627)ELV039904148 (ELSEVIER)S0003-2697(14)00568-5 DE-627 ger DE-627 rakwb eng 570 540 570 DE-600 540 DE-600 550 VZ 333.7 VZ 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Vanderpool, Darin verfasserin aut Residence time and kinetic efficiency analysis of extracellular signal-regulated kinase 2 inhibitors 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. ERK2 Elsevier Time-dependent inhibition Elsevier Residence time Elsevier Kinetic efficiency Elsevier Off-rate Elsevier Structure–kinetic relationship Elsevier Grimshaw, Charles E. oth Lawson, J. David oth Ermolieff, Jacques oth Enthalten in Elsevier Kroon, Frederieke J. ELSEVIER Informing policy to protect coastal coral reefs: Insight from a global review of reducing agricultural pollution to coastal ecosystems 2014 methods in the biological sciences San Diego, Calif (DE-627)ELV018040411 volume:473 year:2015 day:15 month:03 pages:46-52 extent:7 https://doi.org/10.1016/j.ab.2014.12.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA 44.40 Pharmazie Pharmazeutika VZ AR 473 2015 15 0315 46-52 7 045F 570 |
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10.1016/j.ab.2014.12.008 doi GBVA2015019000030.pica (DE-627)ELV039904148 (ELSEVIER)S0003-2697(14)00568-5 DE-627 ger DE-627 rakwb eng 570 540 570 DE-600 540 DE-600 550 VZ 333.7 VZ 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Vanderpool, Darin verfasserin aut Residence time and kinetic efficiency analysis of extracellular signal-regulated kinase 2 inhibitors 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. ERK2 Elsevier Time-dependent inhibition Elsevier Residence time Elsevier Kinetic efficiency Elsevier Off-rate Elsevier Structure–kinetic relationship Elsevier Grimshaw, Charles E. oth Lawson, J. David oth Ermolieff, Jacques oth Enthalten in Elsevier Kroon, Frederieke J. ELSEVIER Informing policy to protect coastal coral reefs: Insight from a global review of reducing agricultural pollution to coastal ecosystems 2014 methods in the biological sciences San Diego, Calif (DE-627)ELV018040411 volume:473 year:2015 day:15 month:03 pages:46-52 extent:7 https://doi.org/10.1016/j.ab.2014.12.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA 44.40 Pharmazie Pharmazeutika VZ AR 473 2015 15 0315 46-52 7 045F 570 |
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10.1016/j.ab.2014.12.008 doi GBVA2015019000030.pica (DE-627)ELV039904148 (ELSEVIER)S0003-2697(14)00568-5 DE-627 ger DE-627 rakwb eng 570 540 570 DE-600 540 DE-600 550 VZ 333.7 VZ 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Vanderpool, Darin verfasserin aut Residence time and kinetic efficiency analysis of extracellular signal-regulated kinase 2 inhibitors 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. ERK2 Elsevier Time-dependent inhibition Elsevier Residence time Elsevier Kinetic efficiency Elsevier Off-rate Elsevier Structure–kinetic relationship Elsevier Grimshaw, Charles E. oth Lawson, J. David oth Ermolieff, Jacques oth Enthalten in Elsevier Kroon, Frederieke J. ELSEVIER Informing policy to protect coastal coral reefs: Insight from a global review of reducing agricultural pollution to coastal ecosystems 2014 methods in the biological sciences San Diego, Calif (DE-627)ELV018040411 volume:473 year:2015 day:15 month:03 pages:46-52 extent:7 https://doi.org/10.1016/j.ab.2014.12.008 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA 44.40 Pharmazie Pharmazeutika VZ AR 473 2015 15 0315 46-52 7 045F 570 |
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Enthalten in Informing policy to protect coastal coral reefs: Insight from a global review of reducing agricultural pollution to coastal ecosystems San Diego, Calif volume:473 year:2015 day:15 month:03 pages:46-52 extent:7 |
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The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. |
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The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. |
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The RAS/RAF/MEK/ERK signal transduction cascade plays an important role in the regulation of critical cellular processes such as cell proliferation, migration, and differentiation. The up-regulation of this pathway can negatively affect cell homeostasis and is responsible for the development of various forms of cancer and inflammation processes. Therefore, there is a strong interest in pursuing drug programs targeting some of the enzymes involved in this pathway. In addition to the determination of K i, K d, IC50, and/or EC50, a more thorough kinetic analysis can provide useful information for the selection of the best lead series during the early stage of the drug discovery process. This study describes a medium-throughput fluorescent probe displacement assay for the rapid determination of the k off constant, residence time, and kinetic efficiency for ERK (extracellular signal-regulated kinase) inhibitors. Using this method, we have identified several inhibitors that we have subjected to further kinetic analysis by comparing k off constants determined for these time-dependent inhibitors using either the active or inactive form of ERK2. |
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