Dapansutrile information

Dapansutrile
Names
	Preferred IUPAC name 3-(Methanesulfonyl)propanenitrile
Identifiers
CAS Number	54863-37-5;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL3989943;
ChemSpider	14967771;
DrugBank	DB16130;
ECHA InfoCard	100.255.888
EC Number	821-352-9;
IUPHAR/BPS	10056;
KEGG	D10920;
PubChem CID	12714644;
UNII	2Z03364G96;
	InChI InChI=1S/C4H7NO2S/c1-8(6,7)4-2-3-5/h2,4H2,1H3 Key: LQFRYKBDZNPJSW-UHFFFAOYSA-N;
	SMILES CS(=O)(=O)CCC#N;
Properties
Chemical formula	C4H7NO2S
Molar mass	133.17 g·mol−1
Hazards
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H302, H315, H319, H335
Precautionary statements	P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Dapansutrile (OLT1177) is an inhibitor of the NLRP3 (nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3) inflammasome.^[1]

An inflammasome can be defined as an immune system receptor that induces inflammation through the activation of caspase 1 and caspase 11 when it is triggered by damaged cells, microbial pathogens, and stress.^[3] NLRP3 is a canonical inflammasome.^[3] The NLRP3 inflammasome comprises NLRP3, the apoptosis spec-like protein (ASC) and the caspase-1^[2] (Figure 1). The NLRP3 inflammasome forms by binding to pattern recognition receptors (PRRs) and damage associated molecular patterns (DAMPS) that activate caspase 1 which then signals for the secretion of pro-inflammatory cytokines IL-1β and IL-18 resulting in pyroptosis^[3]^[4]^[5] Constant activation of the NLRP3 inflammasome is believed to play a direct or indirect role in acute arthritis, atherosclerosis and various neurodegenerative diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD)^[6]^,^[2]^,.^[7] This drug was developed by Olactec Therapeutics with the purpose of decreasing IL-1β peripheral inflammation by binding to the NLRP3 protein and inhibiting the formation of the NLRP3 inflammasome. Interestingly, dapansutrile has also been found to reduce levels of pro inflammatory cytokines IL-18 without interfering with TNF-α levels.^[1] Stressed cells in the system can ignite the NLRP3 inflammasome which in turn produces the secretion inflammatory cytokines such as IL-1β and IL-18. Dapansutrile has tested in clinical trials and has been proposed as a beneficial compound for the remedy of osteoarthritis, and gouty arthritis.^[1] Nevertheless, other preclinical research has proposed dapansutrile to be potentially beneficial for heart failure and multiple sclerosis.^[1]

^ ^a ^b ^c ^d "Dapansutrile" (PDF). Alzheimer's Drug Discovery Foundation. Archived (PDF) from the original on 2021-08-22.
^ ^a ^b ^c Silvis, Max J. M.; Demkes, Evelyne J.; Fiolet, Aernoud T. L.; Dekker, Mirthe; Bosch, Lena; van Hout, Gerardus P. J.; Timmers, Leo; de Kleijn, Dominique P. V. (2020-07-09). "Immunomodulation of the NLRP3 Inflammasome in Atherosclerosis, Coronary Artery Disease, and Acute Myocardial Infarction". Journal of Cardiovascular Translational Research. 14 (1): 23–34. doi:10.1007/s12265-020-10049-w. ISSN 1937-5395. PMC 7892681. PMID 32648087.
^ ^a ^b ^c Lamkanfi, Mohamed; Dixit, Vishva M. (2014-05-22). "Mechanisms and Functions of Inflammasomes". Cell. 157 (5): 1013–1022. doi:10.1016/j.cell.2014.04.007. ISSN 0092-8674. PMID 24855941.
^ Swanson, Karen V.; Deng, Meng; Ting, Jenny P.-Y. (August 2019). "The NLRP3 inflammasome: molecular activation and regulation to therapeutics". Nature Reviews Immunology. 19 (8): 477–489. doi:10.1038/s41577-019-0165-0. ISSN 1474-1741. PMC 7807242. PMID 31036962.
^ Zheng, Danping; Liwinski, Timur; Elinav, Eran (2020-06-09). "Inflammasome activation and regulation: toward a better understanding of complex mechanisms". Cell Discovery. 6 (1): 36. doi:10.1038/s41421-020-0167-x. ISSN 2056-5968. PMC 7280307. PMID 32550001.
^ Marchetti, Carlo; Swartzwelter, Benjamin; Koenders, Marije I.; Azam, Tania; Tengesdal, Isak W.; Powers, Nick; de Graaf, Dennis M.; Dinarello, Charles A.; Joosten, Leo A. B. (December 2018). "NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis". Arthritis Research & Therapy. 20 (1): 169. doi:10.1186/s13075-018-1664-2. ISSN 1478-6362. PMC 6091035. PMID 30075804.
^ Guan, Yadi; Han, Fang (2020). "Key Mechanisms and Potential Targets of the NLRP3 Inflammasome in Neurodegenerative Diseases". Frontiers in Integrative Neuroscience. 14: 37. doi:10.3389/fnint.2020.00037. ISSN 1662-5145. PMC 7393579. PMID 32792920.

[:0-1] "Dapansutrile" (PDF). Alzheimer's Drug Discovery Foundation. Archived (PDF) from the original on 2021-08-22.

[:13-2] Silvis, Max J. M.; Demkes, Evelyne J.; Fiolet, Aernoud T. L.; Dekker, Mirthe; Bosch, Lena; van Hout, Gerardus P. J.; Timmers, Leo; de Kleijn, Dominique P. V. (2020-07-09). "Immunomodulation of the NLRP3 Inflammasome in Atherosclerosis, Coronary Artery Disease, and Acute Myocardial Infarction". Journal of Cardiovascular Translational Research. 14 (1): 23–34. doi:10.1007/s12265-020-10049-w. ISSN 1937-5395. PMC 7892681. PMID 32648087.

[:1-3] Lamkanfi, Mohamed; Dixit, Vishva M. (2014-05-22). "Mechanisms and Functions of Inflammasomes". Cell. 157 (5): 1013–1022. doi:10.1016/j.cell.2014.04.007. ISSN 0092-8674. PMID 24855941.

[4] Swanson, Karen V.; Deng, Meng; Ting, Jenny P.-Y. (August 2019). "The NLRP3 inflammasome: molecular activation and regulation to therapeutics". Nature Reviews Immunology. 19 (8): 477–489. doi:10.1038/s41577-019-0165-0. ISSN 1474-1741. PMC 7807242. PMID 31036962.

[:11-5] Zheng, Danping; Liwinski, Timur; Elinav, Eran (2020-06-09). "Inflammasome activation and regulation: toward a better understanding of complex mechanisms". Cell Discovery. 6 (1): 36. doi:10.1038/s41421-020-0167-x. ISSN 2056-5968. PMC 7280307. PMID 32550001.

[:8-6] Marchetti, Carlo; Swartzwelter, Benjamin; Koenders, Marije I.; Azam, Tania; Tengesdal, Isak W.; Powers, Nick; de Graaf, Dennis M.; Dinarello, Charles A.; Joosten, Leo A. B. (December 2018). "NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis". Arthritis Research & Therapy. 20 (1): 169. doi:10.1186/s13075-018-1664-2. ISSN 1478-6362. PMC 6091035. PMID 30075804.

[7] Guan, Yadi; Han, Fang (2020). "Key Mechanisms and Potential Targets of the NLRP3 Inflammasome in Neurodegenerative Diseases". Frontiers in Integrative Neuroscience. 14: 37. doi:10.3389/fnint.2020.00037. ISSN 1662-5145. PMC 7393579. PMID 32792920.