Assay Implementation: Meng Wu Ph.D., Melissa Miller, Amy Scott M.S., Shunyou Long M.S., Kaiping Xu M.S., Bill Shi Ph.D., David Meyers Ph.D., Jia Xu Ph.D. ..more
Target
| Sequence: alternatively spliced Trp4 [Mus musculus] Description ..   Protein Family: Transient receptor ion channel II Gene:TRPC4 Related Protein 3D Structures |
Depositor Specified Assays
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| AID | Name | Type | Comment |
|---|---|---|---|
| 2247 | Primary cell-based screen for identification of compounds that inhibit transient receptor potential cation channel C4 (TRPC4). | screening | Primary HTS assay for 304007 compounds, among them 1189 are active. |
| 2636 | Confirmatory screen for identification of compounds that inhibit transient receptor potential cation channel C4 (TRPC4) | screening | Confirmatory screen of TRPC4 inhibitors with 2267 compounds tested in duplicates at the concentration of 10 uM, and 735 of them are active. |
| 2637 | Second confirmatory screen for identification of compounds that inhibit transient receptor potential cation channel C4 (TRPC4) | screening | Confirmatory screen of TRPC4 inhibitors with 2267 compounds tested in duplicates at the concentration of 1 uM, and 334 of them are active. |
| 434942 | Confirmation dose response assay for compounds that inhibit transient receptor potential cation channel C4 (TRPC4) | confirmatory | Dose response assay for TRPC4 inhibitors with 2267 compounds, and 753 are active. |
| 434948 | Specificity screen against TRPC6 for compounds that inhibit transient receptor potential cation channel C4 (TRPC4) | screening | Counter screen assay against TRPC6 for TRPC4 inhibitors with 2267 compounds tested, and 108 of them are active. |
| 434978 | Second counter screen for compounds that inhibit transient receptor potential cation channel C4 (TRPC4) | screening | Counter screen assay using the serotonin receptor 5HT1a in place of the mu-Opioid receptor for TRPC4 inhibitors with 2267 compounds tested and 541 of them are active. |
| 492981 | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4) in TRPC6 expressing cells: MPD Assay | screening | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4) in TRPC6 expressing cells: MPD Assay |
| 492983 | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): Manual Electrophysiology | other | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): Manual Electrophysiology |
| 492987 | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4) in TRPC6 expressing cells: MPD Assay CRC | confirmatory | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4) in TRPC6 expressing cells: MPD Assay CRC |
| 492988 | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): Primary HTS assay | screening | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): Primary HTS assay |
| 492991 | SAR Analysis for the identification of selective inhibits of the transient receptor potential cation channel C4 (TRPC4): Automated Electrophysiology | confirmatory | SAR Analysis for the identification of selective inhibits of the transient receptor potential cation channel C4 (TRPC4): Automated Electrophysiology |
| 492994 | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): Primary HTS assay CRC | confirmatory | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): Primary HTS assay CRC |
| 492995 | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): TRPC4 Serotonin Receptor CRC MPD assay | confirmatory | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): TRPC4 Serotonin Receptor CRC MPD assay |
| 492996 | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): ACh assay CRC | confirmatory | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C4 (TRPC4): ACh assay CRC |
| 504589 | SAR Analysis for the identification of selective inhibits of the transient receptor potential cation channel C4 (TRPC4): Automated Electrophysiology_2 | confirmatory | SAR Analysis for the identification of selective inhibits of the transient receptor potential cation channel C4 (TRPC4): Automated Electrophysiology_2 |
| 504554 | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C6 (TRPC6) in cells expressing TRPC4: C4 assay CRC | confirmatory | |
| 504866 | SAR Analysis for the identification of selective inhibitors of the transient receptor potential cation channel C6 (TRPC6) in cells expressing TRPC4: C4 assay CRC 2 | confirmatory |
Description:
Source (MLPCN Center Name): Johns Hopkins Ion Channel Center (JHICC)
Center Affiliation: Johns Hopkins University, School of Medicine
Screening Center PI: Min Li, Ph.D.
Assay Provider: Michael Zhu, Ph.D., Ohio State University
Network: Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Proposal Number: 1 R21 NS056942-01
Grant Proposal PI: Michael Zhu, Ph.D., Ohio State University
Assay Implementation: Meng Wu Ph.D., Melissa Miller, Amy Scott M.S., Shunyou Long M.S., Kaiping Xu M.S., Bill Shi Ph.D., David Meyers Ph.D., Jia Xu Ph.D.
Name: Primary cell-based screen for identification of compounds that inhibit transient receptor potential cation channel C4 (TRPC4).
Description:
Transient receptor potential (TRP) channels act as key regulators of many sensory systems including those for thermo-, photo-, and osmosensation [1-3]. A diversity of biological disorders has been linked to TRP channel malfunction ranging from neuropathic pain [4], cardiovascular diseases [5], to other diseases involving sensory physiology [6,7].
The TRP family of cation channels can be separated into seven subtypes according to structural similarity. Members of this family are nonselective cation channels that allow entry of extracellular calcium into cells resulting in a depolarization of membrane potential [8]. The mammalian TRPC (canonical) subfamily is proposed to function as store and second-messenger operated cation channels [9]. Disruption of TRPC may cause aberrant modulation of intracellular calcium and changes in membrane potential leading to activation of transcription factors, apoptosis, vascular contractility, platelet activation, and cardiac hypertrophy. Currently there are few pharmacological modulators of the TRPC family and no compounds known to target specific TRPC isoforms [10].
This assay summarizes the efforts in identification of test compounds
that inhibit transient receptor potential cation channel C4 (TRPC4). It is still ongoing at JHICC.
References:
1. Venkatachalam, K., and Montell, C. TRP Channels. Annual Review of Biochemistry 76(1), 387-417 (2007) PMID: 17579562
2. Clapham, D., Julius, D., Montell, C. and Schultz, G. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacological Reviews 57(4), 427-450 (2005) PMID: 16382100
3. Reaves, B. J., and Wolstenholme, A. J. The TRP channel superfamily: insights into how structure, protein-lipid interactions and localization influence function. Biochemical Society Transactions 035(1), 77-80 (2007) PMID: 17233605
4. Patapoutian, A., Tate, S., and Woolf, C. J. Transient receptor potential channels: targeting pain at the source. Nat Rev Drug Discov 8(1), 55-68 (2009) PMID: 19116627
5. Vassort G, Alvarez J. Transient receptor potential: a large family of new channels of which several are involved in cardiac arrhythmia. Can J Physiol Pharmacol. 2009 Feb;87(2):100-7.PMID: 19234573
6. Nilius, B. TRP channels in disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1772(8), 805-812 (2007) PMID: 17368864
7. Woudenberg-Vrenken, T. E., Bindels, R. J. M., and Hoenderop, J. G. J. The role of transient receptor potential channels in kidney disease. Nat Rev Nephrol 5(8), 441-449 (2009) PMID: 19546862
8. Zhu, X., Jiang, M., Peyton, M., et al. trp, a Novel Mammalian Gene Family Essential for Agonist-Activated Capacitative Ca2+ Entry. Cell 85(5), 661-671 (1996) PMID: 8646775
9. Abramowitz, J., and Birnbaumer, L. Physiology and pathophysiology of canonical transient receptor potential channels. FASEB J. 23(2), 297-328 (2009) PMID: 18940894
10. Okuhara, D. Y., Hsia, A. Y., and Xie, M. Transient receptor potential channels as drug targets. Expert Opinion on Therapeutic Targets 11(3), 391-401 (2007) PMID: 17298296
Center Affiliation: Johns Hopkins University, School of Medicine
Screening Center PI: Min Li, Ph.D.
Assay Provider: Michael Zhu, Ph.D., Ohio State University
Network: Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Proposal Number: 1 R21 NS056942-01
Grant Proposal PI: Michael Zhu, Ph.D., Ohio State University
Assay Implementation: Meng Wu Ph.D., Melissa Miller, Amy Scott M.S., Shunyou Long M.S., Kaiping Xu M.S., Bill Shi Ph.D., David Meyers Ph.D., Jia Xu Ph.D.
Name: Primary cell-based screen for identification of compounds that inhibit transient receptor potential cation channel C4 (TRPC4).
Description:
Transient receptor potential (TRP) channels act as key regulators of many sensory systems including those for thermo-, photo-, and osmosensation [1-3]. A diversity of biological disorders has been linked to TRP channel malfunction ranging from neuropathic pain [4], cardiovascular diseases [5], to other diseases involving sensory physiology [6,7].
The TRP family of cation channels can be separated into seven subtypes according to structural similarity. Members of this family are nonselective cation channels that allow entry of extracellular calcium into cells resulting in a depolarization of membrane potential [8]. The mammalian TRPC (canonical) subfamily is proposed to function as store and second-messenger operated cation channels [9]. Disruption of TRPC may cause aberrant modulation of intracellular calcium and changes in membrane potential leading to activation of transcription factors, apoptosis, vascular contractility, platelet activation, and cardiac hypertrophy. Currently there are few pharmacological modulators of the TRPC family and no compounds known to target specific TRPC isoforms [10].
This assay summarizes the efforts in identification of test compounds
that inhibit transient receptor potential cation channel C4 (TRPC4). It is still ongoing at JHICC.
References:
1. Venkatachalam, K., and Montell, C. TRP Channels. Annual Review of Biochemistry 76(1), 387-417 (2007) PMID: 17579562
2. Clapham, D., Julius, D., Montell, C. and Schultz, G. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacological Reviews 57(4), 427-450 (2005) PMID: 16382100
3. Reaves, B. J., and Wolstenholme, A. J. The TRP channel superfamily: insights into how structure, protein-lipid interactions and localization influence function. Biochemical Society Transactions 035(1), 77-80 (2007) PMID: 17233605
4. Patapoutian, A., Tate, S., and Woolf, C. J. Transient receptor potential channels: targeting pain at the source. Nat Rev Drug Discov 8(1), 55-68 (2009) PMID: 19116627
5. Vassort G, Alvarez J. Transient receptor potential: a large family of new channels of which several are involved in cardiac arrhythmia. Can J Physiol Pharmacol. 2009 Feb;87(2):100-7.PMID: 19234573
6. Nilius, B. TRP channels in disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1772(8), 805-812 (2007) PMID: 17368864
7. Woudenberg-Vrenken, T. E., Bindels, R. J. M., and Hoenderop, J. G. J. The role of transient receptor potential channels in kidney disease. Nat Rev Nephrol 5(8), 441-449 (2009) PMID: 19546862
8. Zhu, X., Jiang, M., Peyton, M., et al. trp, a Novel Mammalian Gene Family Essential for Agonist-Activated Capacitative Ca2+ Entry. Cell 85(5), 661-671 (1996) PMID: 8646775
9. Abramowitz, J., and Birnbaumer, L. Physiology and pathophysiology of canonical transient receptor potential channels. FASEB J. 23(2), 297-328 (2009) PMID: 18940894
10. Okuhara, D. Y., Hsia, A. Y., and Xie, M. Transient receptor potential channels as drug targets. Expert Opinion on Therapeutic Targets 11(3), 391-401 (2007) PMID: 17298296
Protocol
Please see the related bioassay (AID: 2247) for details of the protocol.
Comment
Result of this screening campaign has yielded a probe compound, ML204.
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| Score | The BioAssay activity ranking score |  | Integer | |||
| 1 | ML# | Molecular library probe number | String |
Additional Information
Grant Number: 1 R21 NS056942-01
Data Table (Concise)
Classification
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