Almorexant hydrochloride (ACT 078573 hydrochloride) is an orally active dual orexin receptor antagonist that blocks the intracellular Ca2+ signaling pathway and, to a certain extent, blocks the excitatory effects of methamphetamine. Almorexant hydrochloride Induces apoptosis and can be used to study sleep disorders.

OX1:1.3 nM(ki), OX2:0.17 nM(ki)

AsPC-1 cells preincubated or not with the SHP2 inhibitor NSC-87877 (50 μM) were challenged for 5 min without or with 1 μM orexin-A or 1 μM Almorexant hydrochloride. In parallel, HPAF-II cells were also challenged for 5 min without or with 1 μM orexin-A. Orexin-A and Almorexant hydrochloride promote tyrosine phosphorylation of SHP2/OX1R complex. [1]

Daily intraperitoneal injection of Almorexant hydrochloride (1.8 μmol/kg) at day 0 in mice xenografted with AsPC-1 cells and up to the mice sacrifices resulted in a significant decrease in tumor volume (> 50%), as compared to untreated mice. Treatment with Almorexant hydrochloride started after AsPC-1 tumors were developed, rapidly and strongly reduced the volume of established tumors. OX1R expression revealed by immunodetection was not affected by Almorexant hydrochloride treatment. [1]