Lycorine Hydrochloride Thioester

Poisoning in small animals represents an ongoing hazard and therapeutic problem in veterinary medicine. Therapeutic induction of emesis in time enables a fast elimination of a toxic compound resulting in a shortened course of poisoning and a higher safety level thereafter, which decisively improves prognosis and treatment. Lycorine is a reliable emetic drug in beagle dogs without serious side effects thought to be more beneficial in tolerability and efficacy than the rarely used apomorphine. Therefore, this study investigates efficacy and tolerability of differently composed potential drug formulations of lycorine hydrochloride for s.c. administration in dogs as an emetic principle. By emesis response analysis four dimethyl sulfoxide (DMSO)-based active pharmaceutical ingredient (API) formulations were favored. Two of them (F5 and F6) qualified for further drug development. Both formulations ensure a safe pharmacologically induced emesis within about 30 min after injection, suitable for use as an in time decontaminant in acute poisoning of dogs. DMSO-based formulations were well tolerated and offer a novel promising strategy for treatment of poisoning.

Although small‐cell lung cancer (SCLC) accounts for a small fraction of lung cancer cases (~15%), the prognosis of patients with SCLC is poor with an average overall survival period of a few months without treatment. Current treatments include standard chemotherapy, which has minimal efficacy and a newly developed immunotherapy that thus far, benefits a limited number of patients. In the current study, we screened a natural product library and identified 5 natural compounds, in particular tubercidin and lycorine HCl, that display prominent anti‐SCLC activities in vitro and in vivo. Subsequent RNA‐sequencing and functional validation assays revealed the anti‐SCLC mechanisms of these new compounds, and further identified new cellular factors such as BCAT1 as a potential therapeutic target with clinical implication in SCLC patients. Taken together, our study provides promising new directions for fighting this aggressive lung cancer.