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Among these kinases, GSK-3\u03b2 plays the most crucial role. In this study, we present compound 62, a novel, remarkably potent, competitive GSK-3\u03b2 inhibitor (IC50 = 8 nM, Ki = 2 nM) that also exhibits additional ROCK-1 inhibitory activity (IC50 = 2.3 \u00b5M) and demonstrates anti-inflammatory and neuroprotective properties. Compound 62 effectively suppresses the production of nitric oxide (NO) and pro-inflammatory cytokines in the lipopolysaccharide-induced model of inflammation in the microglial BV-2 cell line. Furthermore, it shows neuroprotective effects in an okadaic-acid-induced tau hyperphosphorylation cell model of neurodegeneration. The compound also demonstrates the potential for further development, characterized by its chemical and metabolic stability in mouse microsomes and fair solubility.<\/jats:p>","DOI":"10.3390\/molecules29112616","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T05:58:00Z","timestamp":1717394280000},"page":"2616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Connecting GSK-3\u03b2 Inhibitory Activity with IKK-\u03b2 or ROCK-1 Inhibition to Target Tau Aggregation and Neuroinflammation in Alzheimer\u2019s Disease\u2014Discovery, In Vitro and In Cellulo Activity of Thiazole-Based Inhibitors"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-5663","authenticated-orcid":false,"given":"Izabella","family":"G\u00f3ral","sequence":"first","affiliation":[{"name":"Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"},{"name":"Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 16 Lazarza St., 31-530 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2504-1939","authenticated-orcid":false,"given":"Tomasz","family":"Wichur","sequence":"additional","affiliation":[{"name":"Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5355-577X","authenticated-orcid":false,"given":"Emilia","family":"S\u0142ugocka","sequence":"additional","affiliation":[{"name":"Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"},{"name":"Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 16 Lazarza St., 31-530 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0295-2772","authenticated-orcid":false,"given":"Justyna","family":"Gody\u0144","sequence":"additional","affiliation":[{"name":"Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-5115","authenticated-orcid":false,"given":"Natalia","family":"Sza\u0142aj","sequence":"additional","affiliation":[{"name":"Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5037-6183","authenticated-orcid":false,"given":"Paula","family":"Zar\u0119ba","sequence":"additional","affiliation":[{"name":"Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1632-6569","authenticated-orcid":false,"given":"Monika","family":"G\u0142uch-Lutwin","sequence":"additional","affiliation":[{"name":"Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7906-0353","authenticated-orcid":false,"given":"Barbara","family":"Mordyl","sequence":"additional","affiliation":[{"name":"Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3211-7188","authenticated-orcid":false,"given":"Dawid","family":"Panek","sequence":"additional","affiliation":[{"name":"Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-170X","authenticated-orcid":false,"given":"Anna","family":"Wi\u0119ckowska","sequence":"additional","affiliation":[{"name":"Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2022). 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