In vivo photocontrol of orexin receptors with a nanomolar light-regulated analogue of orexin-B.

Orexinergic neurons are critically involved in regulating arousal, wakefulness, and appetite. Their dysfunction has been associated with sleeping disorders, and non-peptide drugs are currently being developed to treat insomnia and narcolepsy. Yet, no light-regulated agents are available to reversibly control their activity.

Photoswitchable Carbamazepine Analogs for Non-Invasive Neuroinhibition In Vivo.

A problem of systemic pharmacotherapy is off-target activity, which causes adverse effects. Outstanding examples include neuroinhibitory medications like antiseizure drugs, which are used against epilepsy and neuropathic pain but cause systemic side effects. There is a need of drugs that inhibit nerve signals locally and on-demand without affecting other regions of the body.

Arylazobenzimidazoles: versatile visible-light photoswitches with tuneable -isomer stability.

Benzimidazole heterocycles are of great importance in medicinal chemistry due to their applicability to a wide range of pharmacological targets, therefore representing a prototypical "privileged structure". In photopharmacology, azoheteroarene photoswitches have emerged as valuable tools for a variety of applications due to the high tuneability of their photophysical properties. Benzimidazole-based photoswitches could therefore enable the optically-controlled investigation of many pharmacological targets and find application in materials science.

Light-dependent inhibition of clathrin-mediated endocytosis in yeast unveils conserved functions of the AP2 complex.

Clathrin-mediated endocytosis (CME) is an essential cellular process, conserved among eukaryotes. Yeast constitutes a powerful genetic model to dissect the complex endocytic machinery, yet there is a lack of specific pharmacological agents to interfere with CME in these organisms. TL2 is a light-regulated peptide inhibitor targeting the AP2-β-adaptin/β-arrestin interaction and that can photocontrol CME with high spatiotemporal precision in mammalian cells.