Identification of the new candidate NLRP3 inhibitor using combined computational approach
Апстракт
The NOD-like receptor pyrin domain-containing protein 3 (NLRP3), an important
intracellular sensor in the innate immune system, detects a plethora of exogenous and
endogenous stimuli, leading to inflammasome formation and caspase-1 activation. More
recently, it emerged as an attractive drug target due to abnormal NLRP3 inflammasome
activation implicated in many acute and chronic diseases (including diabetes,
atherosclerosis, metabolic syndrome, cardiovascular, and neurodegenerative diseases)
[1]. Several direct NLRP3 inhibitors that block its ATPase activity by keeping it in
closed conformation have been reported [1,2]. Some of them have entered clinical trials,
but still, none of them is FDA approved.
A powerful strategy in identifying potential NLRP3 inhibitors can be in silico drug
repurposing of compounds with already known safety profiles. In this study, we
performed a virtual screening protocol that considers both long- and short-range
interactions between molecules. ...First, the Informational spectrum method developed for
small molecules was applied for searching the Drugbank database. Selected candidates
were filtered by successive cross-correlation spectra analysis. Finally, after molecular
docking, we identified the most promising candidate and proposed it for further
experimental testing.
Извор:
9th Conference of Young Chemists of Serbia, 2023, 50-Издавач:
- 9th Conference of Young Chemists of Serbia
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200017 (Универзитет у Београду, Институт за нуклеарне науке Винча, Београд-Винча) (RS-MESTD-inst-2020-200017)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
Напомена:
- Book of Abstracts: 9th Conference of Young Chemists of Serbia Novi Sad, 4th November 2023
URI
https://www.chem.bg.ac.rs/pz/news1.py?q=3820&l=1https://imagine.imgge.bg.ac.rs/handle/123456789/2206
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Stevanović, Kristina AU - Senćanski, Milan AU - Perović, Vladimir AU - Glišić, Sanja PY - 2023 UR - https://www.chem.bg.ac.rs/pz/news1.py?q=3820&l=1 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2206 AB - The NOD-like receptor pyrin domain-containing protein 3 (NLRP3), an important intracellular sensor in the innate immune system, detects a plethora of exogenous and endogenous stimuli, leading to inflammasome formation and caspase-1 activation. More recently, it emerged as an attractive drug target due to abnormal NLRP3 inflammasome activation implicated in many acute and chronic diseases (including diabetes, atherosclerosis, metabolic syndrome, cardiovascular, and neurodegenerative diseases) [1]. Several direct NLRP3 inhibitors that block its ATPase activity by keeping it in closed conformation have been reported [1,2]. Some of them have entered clinical trials, but still, none of them is FDA approved. A powerful strategy in identifying potential NLRP3 inhibitors can be in silico drug repurposing of compounds with already known safety profiles. In this study, we performed a virtual screening protocol that considers both long- and short-range interactions between molecules. First, the Informational spectrum method developed for small molecules was applied for searching the Drugbank database. Selected candidates were filtered by successive cross-correlation spectra analysis. Finally, after molecular docking, we identified the most promising candidate and proposed it for further experimental testing. PB - 9th Conference of Young Chemists of Serbia C3 - 9th Conference of Young Chemists of Serbia T1 - Identification of the new candidate NLRP3 inhibitor using combined computational approach SP - 50 SP - 50 UR - https://hdl.handle.net/21.15107/rcub_imagine_2206 ER -
@conference{ author = "Stevanović, Kristina and Senćanski, Milan and Perović, Vladimir and Glišić, Sanja", year = "2023", abstract = "The NOD-like receptor pyrin domain-containing protein 3 (NLRP3), an important intracellular sensor in the innate immune system, detects a plethora of exogenous and endogenous stimuli, leading to inflammasome formation and caspase-1 activation. More recently, it emerged as an attractive drug target due to abnormal NLRP3 inflammasome activation implicated in many acute and chronic diseases (including diabetes, atherosclerosis, metabolic syndrome, cardiovascular, and neurodegenerative diseases) [1]. Several direct NLRP3 inhibitors that block its ATPase activity by keeping it in closed conformation have been reported [1,2]. Some of them have entered clinical trials, but still, none of them is FDA approved. A powerful strategy in identifying potential NLRP3 inhibitors can be in silico drug repurposing of compounds with already known safety profiles. In this study, we performed a virtual screening protocol that considers both long- and short-range interactions between molecules. First, the Informational spectrum method developed for small molecules was applied for searching the Drugbank database. Selected candidates were filtered by successive cross-correlation spectra analysis. Finally, after molecular docking, we identified the most promising candidate and proposed it for further experimental testing.", publisher = "9th Conference of Young Chemists of Serbia", journal = "9th Conference of Young Chemists of Serbia", title = "Identification of the new candidate NLRP3 inhibitor using combined computational approach", pages = "50-50", url = "https://hdl.handle.net/21.15107/rcub_imagine_2206" }
Stevanović, K., Senćanski, M., Perović, V.,& Glišić, S.. (2023). Identification of the new candidate NLRP3 inhibitor using combined computational approach. in 9th Conference of Young Chemists of Serbia 9th Conference of Young Chemists of Serbia., 50. https://hdl.handle.net/21.15107/rcub_imagine_2206
Stevanović K, Senćanski M, Perović V, Glišić S. Identification of the new candidate NLRP3 inhibitor using combined computational approach. in 9th Conference of Young Chemists of Serbia. 2023;:50. https://hdl.handle.net/21.15107/rcub_imagine_2206 .
Stevanović, Kristina, Senćanski, Milan, Perović, Vladimir, Glišić, Sanja, "Identification of the new candidate NLRP3 inhibitor using combined computational approach" in 9th Conference of Young Chemists of Serbia (2023):50, https://hdl.handle.net/21.15107/rcub_imagine_2206 .