Orexin OX2 receptor agonists have demonstrated the ability to enhance wakefulness in rodent models, as well as in nonhuman primates and patients with narcolepsy and idiopathic hypersomnia. Based on recent findings, it has been hypothesized that they may also regulate cognition, mood and other neuropsychiatric functions. Furthermore, dysregulated orexin signaling has been reported in patients with major depressive disorder (MDD) with suicide attempts.
Acute myeloid leukemia (AML) is a hematological cancer with limited treatment options and characterized by frequent relapse and poor prognosis. The only approved antibody-drug conjugate for AML is gemtuzumab ozogamicin, which targets CD33.
Receptor-interacting protein kinase 1 (RIPK1) helps promote the survival of cancer cells, and degrading it can sensitize tumors to immunotherapy against PD-1. Degrading the entire protein seems to be essential: merely blocking its kinase activity does not sensitize tumors.