AO-365/43472821 is a selective, brain-penetrant Dual-specificity tyrosine phosphorylation-regulated kinase 1A ( DYRK1A ) inhibitor ( IC50 = 0.29 μM) and shows a significant inhibitory effect on ( CDC-like kinase 1) CLK1 ( IC50 = 0.08 μM). AO-365/43472821 could protect the human neuroblastoma cell line SH-SY5Y from Okadaic acid (OA)-induced injury. AO-365/43472821 decreased tau (pSer396)/tau and Aβ1-42 protein expression. AO-365/43472821 can be used for the study of Alzheimer's disease [1].
In Vitro, AO-365/43472821 (Compound Y16-5) (1 μM, 48 h) significantly protects SH-SY5Y cells from OA-induced damage and improves cell survival[1]. AO-365/43472821 (1-10 μM) significantly reduces the tau (pSer 396)/tau level in SH-SY5Y cells in a concentration-dependent manner, and also reduces the expression of Aβ1-42 protein[1]. AO-365/43472821 (48 h) shows a CC50 greater than 100 μM in both SH-SY5Y and HL-7702 cells, indicating no cytotoxicity[1].
References:
[1]. Si X, et al. Computer-aided discovery of triazolothiadiazoles as DYRK1A-targeted neuroprotective agents. RSC Med Chem. 2025 Jul 14.
In Vitro, AO-365/43472821 (Compound Y16-5) (1 μM, 48 h) significantly protects SH-SY5Y cells from OA-induced damage and improves cell survival[1]. AO-365/43472821 (1-10 μM) significantly reduces the tau (pSer 396)/tau level in SH-SY5Y cells in a concentration-dependent manner, and also reduces the expression of Aβ1-42 protein[1]. AO-365/43472821 (48 h) shows a CC50 greater than 100 μM in both SH-SY5Y and HL-7702 cells, indicating no cytotoxicity[1].
References:
[1]. Si X, et al. Computer-aided discovery of triazolothiadiazoles as DYRK1A-targeted neuroprotective agents. RSC Med Chem. 2025 Jul 14.