Endoplasmic reticulum (ER) stress causes neuronal dysfunction followed by cell death

Endoplasmic reticulum (ER) stress causes neuronal dysfunction followed by cell death and is recognized as a feature of many neurodegenerative diseases. against thapsigargin-induced cell death and displays no protection against other insults known to induce cellular stress or activate p38. However compound 4hh provides moderate inhibition of p38 activity stimulated by compounds that disrupt calcium homeostasis. Our data indicate that probe compound 4hh is a valuable small molecule tool that can be used to investigate the effects of ER stress on human neurons. This approach may provide the basis for the future development of therapeutics for the treatment of neurodegenerative diseases. 396 [M + H]+. HRMS calcd for C23H27ClN3O [M + H]+: 396.1837. Found: 396.1838. 7 3 4 5 10 Rabbit Polyclonal to TUBGCP6. 11 [M + H]+. HRMS calcd for C23H24ClN3O [M + H]+: 394.1608. Found: 394.1592. 7 3 4 5 10 11 [M + H]+. HRMS calcd for C24H27ClN3O [M + H]+: 408.1837. Found: 408.1824. 7 3 4 5 10 11 [M + H]+. HRMS calcd for C23H25ClN3O2 [M + H]+: 410.1630. Found: 410.1609. 7 3 4 5 10 11 [M + H]+. HRMS calcd for C27H35ClN3O [M + H]+: 452.2463. Found out: 452.2453. 7 3 4 5 10 Fosaprepitant dimeglumine 11 [M + H]+. HRMS calcd for C21H23BrN3O [M + H]+: 414.1001. Found out: 414.0983. 7 3 4 5 10 11 [M + H]+. HRMS calcd for C23H26BrN3O [M + H]+: 440.1259. Found out: 440.1254. 7 3 4 5 10 11 [M + H]+. HRMS calcd for C24H27BrN3O [M + H]+: 454.1315. Found out: 454.1275. 7 3 4 5 10 11 6.4 Hz 4 2.63 (m 2 2.4 (m 2 2.05 (m 2 1.47 (m 4 1.29 (m 4 0.92 (m 6 13 NMR (100 MHz CDCl3): δ 194.2 153.8 147 136.8 132.1 129.7 128 126.1 122.9 122 114.3 112.4 111.4 56.9 50.7 36.2 32.7 29.4 21.6 20.3 14 ESI-MS 498 [M + H]+. HRMS calcd for C27H35BrN3O [M + H]+: 498.1941. Found out: 498.1932. 11 3 4 5 10 11 [M + H]+. HRMS calcd for C22H22F3N3O [M + H]+: 402.1715. Found out: 402.1716. 11 3 4 5 10 11 6.4 Hz 2 6.23 (s 1 5.86 (s 1 3.23 (q = 4.6 Hz 4 2.8 (m 2 2.42 (m 2 2.2 (m 2 1.06 (t = 4.6 Hz 6 13 NMR (100 MHz CDCl3): δ 194.1 153.6 146.5 140.5 130 127.9 121.2 120.3 114.6 111.6 56.6 44.1 36.2 32.7 21.7 12.5 ESI-MS 430 [M + H]+. HRMS calcd for C24H27F3N3O [M + H]+: 430.2101. Found out: 430.2093. 11 3 4 5 10 11 [M + H]+. HRMS calcd for C24H24F3N3O [M + H]+: 428.1871. Found out: 428.1873. 7 3 3 4 5 10 11 7.8 Hz 1 2.84 (s 6 2.58 (m 1 2.29 (m 3 1.15 (d = 7.8 Hz 3 Fosaprepitant dimeglumine 1.09 (d = 7.8 Hz 3 13 NMR (100 MHz CDCl3): δ 193.9 151.7 149.3 136.2 132 131.5 127.8 125.6 123.4 122.6 119.1 113 112.4 57.3 49.7 46.4 40.6 32.4 28.9 27.6 ESI-MS 396 [M + H]+. HRMS calcd for C23H27ClN3O [M + H]+: 396.1837. Found out: 396.1840. 7 3 3 4 5 10 11 6.9 Hz 4 2.58 (m 1 2.29 (m 3 1.07 (m 12 13 NMR (100 MHz CDCl3): δ 194.0 151.9 146.7 138.7 136.3 131.9 130.3 129.5 Fosaprepitant dimeglumine 128.1 125.4 123.2 122.6 120.8 120.4 119.2 113.1 111.6 57.1 49.7 46.5 44.1 32.4 28.9 27.7 12.5 ESI-MS 424 [M Fosaprepitant dimeglumine + H]+. HRMS calcd for C25H31ClN3O [M + H]+: 424.2150. Found out: 424.2186. 7 3 3 4 5 10 11 [M + H]+. HRMS calcd for C25H29ClN3O [M + H]+: 422.1994 Found: 422. 2021. 7 3 3 4 5 10 11 [M + H]+. HRMS calcd for C26H31ClN3O [M + H]+: 436.2150. Found out: 436.2188. 7 3 3 4 5 10 11 8.2 Hz 1 6.21 (s 1 5.82 (s 1 3.79 (t = 4.1 Hz 4 3.04 (t = 4.1 Hz 4 2.6 (m 1 2.29 (m 3 1.15 (s 3 1.08 (s 3 13 NMR (100 MHz CDCl3): δ 193.9 152 149.8 136 135.1 131.9 127.9 125.7 123.4 122.5 119.2 115.4 112.6 66.9 57.3 49.7 49.2 46.4 32.4 28.8 27.7 ESI-MS 438 [M + H]+. HRMS calcd for C25H29ClN3O2 [M + H]+: 438.1943. Found out: 438.1956. 7 3 3 4 5 10 11 [M + H]+. HRMS calcd for C29H39ClN3O [M + H]+: 480.2776. Found out: 480.2795 7 3 3 4 5 10 11 8.7 Hz 2 6.65 (m 1 6.42 (m 3 6.2 (m 1 5.51 (d = 5.5 Hz 1 2.71 (s 6 2.46 (m 3 2.07 (m 1 1.01 (s 3 0.97 (s 3 13 NMR (100 MHz DMSO-442 [M + H]+. HRMS calcd for C23H27BrN3O [M + H]+: 442.1314. Found out: 442.1298. 7 3 3 4 5 10 11 4.6 Hz 4 2.58 (m 1 2.29 (m 3 1.92 (m 4 1.15 (s 3 1.08 (s 3 13 NMR (100 MHz CDCl3): δ 193.8 151.6 146.7 136.7 132.3 130.3 127.9 126.2 122.8 121.9 113.2 112.6 111.4 57.3 49.7 47.4 46.4 32.4 28.8 27.7 25.3 ESI-MS 468 [M + H]+. HRMS calcd for C25H29BrN3O [M + H]+: 468.1471. Found out: 468.1464. 7 3 3 4 5 10 11 8.2 Hz 2 6.2 (s 1 5.82 (s 1 3.03 (t = 5.5 Hz Fosaprepitant dimeglumine Fosaprepitant dimeglumine 4 2.58 (m 1 2.29 (m 3 1.63 (m 4 1.52 (m 2 1.15 (s 3 1.08 (s 3 13 NMR (100 MHz CDCl3): δ 193.9 152.1 136.5 132.3 127.7 126.3 122.9 121.9 116.4 112.7 57.2 50.4 49.6 46.4 32.3 28.9 27.7 25.8 24.2 ESI-MS 482 [M + H]+. HRMS calcd for C26H31BrN3O [M + H]+: 482.1628. Found out:.