(-)-Englerin†A is a potent and selective activator of TRPC4 and TRPC5 calcium channels.

Current therapies for common types of cancer such as renal cell cancer are often ineffective and unspecific, and novel pharmacological targets and approaches are in high demand. Here we show the unexpected possibility for the rapid and selective killing of renal cancer cells through activation of calcium-permeable nonselective transient receptor potential canonical (TRPC) calcium channels by the sesquiterpene (-)-englerin A. This compound was found to be a highly efficient, fast-acting, potent, selective, and direct stimulator of TRPC4 and TRPC5 channels. TRPC4/5 activation through a high-affinity extracellular (-)-englerin A binding site may open up novel opportunities for drug discovery aimed at renal cancer.

The Contribution of Galenics to Patients' Sensory Perception of Nasal Sprays After Nasal Surgery: Data from a Prospective Randomised, Controlled, Double-Blind, Crossover, Multicentre Study.

INTRODUCTION: Postoperative care after nasal surgery is commonly achieved with nasal sprays. The current study compared two decongesting, wound-healing nasal sprays in patients after nasal surgery in order to investigate their sensory perception. One of the sprays was a new galenic formulation (nasic® neo, Cassella-med GmbH & Co. KG). METHODS: According to the crossover design, patients who had undergone nasal surgery applied two different nasal sprays during two treatment periods of 4 days each, interrupted by a 3-day washout period. Sensory perception of the nasal sprays was assessed with the nasal spray sensoric scale. Throughout the study, nasal obstruction was evaluated by patients, and physical examinations, measurements of vital parameters and rhinoscopic examinations were carried out by investigators. Adverse events were documented during the entire study, and following treatment, patients judged the overall preference, efficacy and tolerability of both products. RESULTS: Overall, no significant differences in sum scores of the assessments of the nasal spray sensoric scale were observed between treatments. A significant period effect observed during the crossover study limited the overall analysis. Nevertheless, significantly more patients preferred the new galenics nasal spray compared to the comparator spray (57.1% vs. 34.7%; p = 0.031). Further, 10% more patients rated the efficacy of the new galenics as 'good' to 'very good' compared to the comparator. Importantly, a subgroup population of patients with more pronounced signs of inflammation present at screening evaluated the sensory perception of the new galenics as significantly better (p = 0.033) compared to the comparator. Within this subgroup, no period effect was observed. The application of both nasal sprays was shown to be safe and well-tolerated. CONCLUSION: The overall sensory perception of both nasal sprays was evaluated comparably well in patients after nasal surgery and overall the application of the new galenics nasal spray was preferred by significantly more patients compared to the comparator nasal spray. Patients with marked nasal abnormalities may have a greater benefit from the contribution of galenics as significant differences in the sensory evaluation by the nasal spray sensoric scale in favour of the new galenics product were shown for this subgroup. TRIAL REGISTRATION: The current study was registered in the EU Clinical Trials Register with the EudraCT No. 2019-004936-52.

Transforming terpene-derived aldehydes into 1,2-epoxides via asymmetric α-chlorination: subsequent epoxide opening with carbon nucleophiles.

Merging Jørgensen's and MacMillan's organocatalytic aldehyde chlorinations enables the synthesis of chiral vinylcyclopropanes and (-)-cis-aerangis lactone via terpene-derived 1,2-epoxides.