LDN-57444

LDN-57444 is a reversible, competitive and site-directed inhibitor of ubiquitin C-terminal hydrolase L1 (UCH-L1), with an IC₅₀ of 0.88 μM and a K_i of 0.40 μM; LDN-57444 also suppresses UCH-L3 activity, with an IC₅₀ of 25 μM. IC50 & Target: IC50: 0.88 μM (UCH-L1), 25 μM (UCH-L3)^[1]
Ki: 0.40 μM (UCH-L1)^[1] In Vitro: LDN-57444 is a reversible, competitive inhibitor of UCH-L1, with an IC₅₀ of 0.88 μM, and also suppresses UCH-L3 activity, with an IC₅₀ of 25 μM^[1]. LDN-57444 (LDN, 5 μM for 1 hr) inhibits 70% of Uch activity in hippocampal slices of the mouse brain. LDN-57444 (5 μM for 2 hr) does not reduce potentiation further in APP/PS1 slices or in wt slices exposed to 200 nM Aβ^[2]. LDN-57444 (25-100 μM) inhibits ubiquitin-proteasome activity dose-dependently in SK-N-SH cells. LDN-57444 (50 μM) also induces apoptotic cell death, causes the endoplasmic reticulum stress and results in expression of spliced XBP-1(XBP-1s, 48KD) in SK-N-SH cells^[3]. In Vivo: LDN-57444 (0.4 mg/kg, i.p.) blocks the beneficial effect of V-Uch-L1, and worsens contextual conditioning performance as the mice are exposed to the context at 1, 7, 14, and 21 days after training^[2].