KU124 (9,10,10-trioxo-N-(2-phenylphenyl)thioxanthene-3-carboxamide) as a novel inhibitor of TASK-1

Ana Dumani¹Annette Jocob¹Diego Chavez¹Abena Amankwaa¹Ramish Zahed¹Martha Julemis¹Hinaben Patel¹Joana Lopez¹Steven Almazan¹Patrick Martins¹Anthony Contreras¹Sofiia Korotka¹Gianna Kiszka¹Alexander Aleynik¹Justin Patino¹David Graham¹Megan Blaisdell¹Youssef Elhowary¹Shuayb Yousuf¹Chelsea Pelley¹Jenna Marciano¹Jessica Best¹Rhustie Valdizno¹Nikki Mastrodomenico¹Jonelle Brown¹Sarah Schwartz²Irene Anin¹Yara Farrag¹Rinchu George¹Gianna Medeiros¹Sophia Lang¹Marilyn Dennis¹Oluwatoni Awoleye¹Lamont Lee¹Ericka Salgado¹Diana Figueroa Chea¹Thomas Walter COMOLLO^1,2*

• ¹Kean University, Union, United States
• ²Touro University, New York City, New York, United States

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 of 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 proposed 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 after targeting the inner vestibule site, we found an active TASK-1 inhibitor. We suspect this region of interest can be exploited to find additional TASK-1 inhibitors. Our initial success lends validity to our virtual screening methodology and parameters. In this research study, we identified a novel TASK-1 inhibitor, KU124, that we verified in an in vitro assay.