KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1
TASK-1 is a two-pore K+ leak channel. The name, TASK-1, stands for TWIK-related acid-sensitive potassium channel 1, and this channel is encoded by the KCNK3 gene. TASK-1 channels are expressed in humans and modulate cell excitability in excitable cells such as neurons, cardiomyocytes, and vascular s...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1577171/full |
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| author | Ana Dumani Annette Jacob Diego Chavez Abena Amankwaa Ramish Zahed Martha Julemis Hinaben Patel Joana Lopez Steven Almazan Patrick Martins Anthony Contreras Sofiia Korotka Gianna Kiszka Alexander Aleynik Justin Patino David Graham Megan Blaisdell Youssef Elhowary Shuayb Yousuf Chelsea Pelley Jenna Marciano Jessica Best Rhustie Valdizno Nikki Mastrodomenico Jonelle Brown Sarah Schwartz Irene Anin Yara Farrag Rinchu George Gianna Medeiros Sophia Lang Marilyn Dennis Oluwatoni Awoleye Lamont Lee Ericka Salgado Diana Figueroa Chea Thomas Walter Comollo Thomas Walter Comollo |
| author_facet | Ana Dumani Annette Jacob Diego Chavez Abena Amankwaa Ramish Zahed Martha Julemis Hinaben Patel Joana Lopez Steven Almazan Patrick Martins Anthony Contreras Sofiia Korotka Gianna Kiszka Alexander Aleynik Justin Patino David Graham Megan Blaisdell Youssef Elhowary Shuayb Yousuf Chelsea Pelley Jenna Marciano Jessica Best Rhustie Valdizno Nikki Mastrodomenico Jonelle Brown Sarah Schwartz Irene Anin Yara Farrag Rinchu George Gianna Medeiros Sophia Lang Marilyn Dennis Oluwatoni Awoleye Lamont Lee Ericka Salgado Diana Figueroa Chea Thomas Walter Comollo Thomas Walter Comollo |
| author_sort | Ana Dumani |
| collection | DOAJ |
| description | TASK-1 is a two-pore K+ leak channel. The name, TASK-1, stands for TWIK-related acid-sensitive potassium channel 1, and this channel is encoded by the KCNK3 gene. TASK-1 channels are expressed in humans and modulate cell excitability in excitable cells such as neurons, cardiomyocytes, and vascular smooth muscle cells. TASK-1 inhibition is a mechanism of action for some respiratory stimulants, such as doxapram. TASK-1 channels have also been suggested to play a role in circumventing cell apoptosis in a population of non-small-cell lung cancer cells. We propose that the inner vestibule of the TASK-1 channel, a known binding site of known TASK-1 inhibitors, BAY10000493 and BAY2341237, can be exploited via virtual screening to find other novel TASK-1 inhibitors. Our results show that by targeting the inner vestibule site, we found an active TASK-1 inhibitor. We suspect that this region of interest can be further exploited to discover additional TASK-1 inhibitors. Our initial success lends validity to our virtual screening methodology and parameters. In this study, we identified a novel TASK-1 inhibitor, KU124, which we verified using an in vitro assay. |
| format | Article |
| id | doaj-art-ffc0224f5e504d5caad5b95675ad4e46 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-ffc0224f5e504d5caad5b95675ad4e462025-08-20T03:24:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15771711577171KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1Ana Dumani0Annette Jacob1Diego Chavez2Abena Amankwaa3Ramish Zahed4Martha Julemis5Hinaben Patel6Joana Lopez7Steven Almazan8Patrick Martins9Anthony Contreras10Sofiia Korotka11Gianna Kiszka12Alexander Aleynik13Justin Patino14David Graham15Megan Blaisdell16Youssef Elhowary17Shuayb Yousuf18Chelsea Pelley19Jenna Marciano20Jessica Best21Rhustie Valdizno22Nikki Mastrodomenico23Jonelle Brown24Sarah Schwartz25Irene Anin26Yara Farrag27Rinchu George28Gianna Medeiros29Sophia Lang30Marilyn Dennis31Oluwatoni Awoleye32Lamont Lee33Ericka Salgado34Diana Figueroa Chea35Thomas Walter Comollo36Thomas Walter Comollo37Kean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesTouro University, New York, NY, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesKean University, Union, NJ, United StatesTouro University, New York, NY, United StatesTASK-1 is a two-pore K+ leak channel. The name, TASK-1, stands for TWIK-related acid-sensitive potassium channel 1, and this channel is encoded by the KCNK3 gene. TASK-1 channels are expressed in humans and modulate cell excitability in excitable cells such as neurons, cardiomyocytes, and vascular smooth muscle cells. TASK-1 inhibition is a mechanism of action for some respiratory stimulants, such as doxapram. TASK-1 channels have also been suggested to play a role in circumventing cell apoptosis in a population of non-small-cell lung cancer cells. We propose that the inner vestibule of the TASK-1 channel, a known binding site of known TASK-1 inhibitors, BAY10000493 and BAY2341237, can be exploited via virtual screening to find other novel TASK-1 inhibitors. Our results show that by targeting the inner vestibule site, we found an active TASK-1 inhibitor. We suspect that this region of interest can be further exploited to discover additional TASK-1 inhibitors. Our initial success lends validity to our virtual screening methodology and parameters. In this study, we identified a novel TASK-1 inhibitor, KU124, which we verified using an in vitro assay.https://www.frontiersin.org/articles/10.3389/fphar.2025.1577171/fullTWIK-related acid-sensitive potassium channel 1virtual screeninginhibitorKU124molecular dynamicsthallium flux |
| spellingShingle | Ana Dumani Annette Jacob Diego Chavez Abena Amankwaa Ramish Zahed Martha Julemis Hinaben Patel Joana Lopez Steven Almazan Patrick Martins Anthony Contreras Sofiia Korotka Gianna Kiszka Alexander Aleynik Justin Patino David Graham Megan Blaisdell Youssef Elhowary Shuayb Yousuf Chelsea Pelley Jenna Marciano Jessica Best Rhustie Valdizno Nikki Mastrodomenico Jonelle Brown Sarah Schwartz Irene Anin Yara Farrag Rinchu George Gianna Medeiros Sophia Lang Marilyn Dennis Oluwatoni Awoleye Lamont Lee Ericka Salgado Diana Figueroa Chea Thomas Walter Comollo Thomas Walter Comollo KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1 Frontiers in Pharmacology TWIK-related acid-sensitive potassium channel 1 virtual screening inhibitor KU124 molecular dynamics thallium flux |
| title | KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1 |
| title_full | KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1 |
| title_fullStr | KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1 |
| title_full_unstemmed | KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1 |
| title_short | KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1 |
| title_sort | ku124 9 10 10 trioxo n 2 phenylphenyl thioxanthene 3 carboxamide as a novel inhibitor of task 1 |
| topic | TWIK-related acid-sensitive potassium channel 1 virtual screening inhibitor KU124 molecular dynamics thallium flux |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1577171/full |
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