Helsinn: 20 years in primary cancer supportive care.

Sergio Cantoreggi speaks to Henry Ireland, Commissioning Editor: Sergio Cantoreggi, PhD, is the Chief Scientific Officer and Global Head of Research and Development of the Helsinn Group, a mid-sized pharmaceutical company headquartered in Lugano, Switzerland, and focused on providing cancer supportive care solutions to oncology patients worldwide. Dr Cantoreggi has overall responsibility for all R&D activities of the Helsinn Group and has contributed to six major regulatory approvals of cancer supportive care agents in the USA, Europe and Japan. Dr Cantoreggi joined Helsinn Healthcare in 2000 as drug development scientist and was appointed Head of R&D in 2005.

In vitro and in vivo pharmacological characterization of the novel NK₁ receptor selective antagonist Netupitant.

The novel NK(1) receptor ligand Netupitant has been characterized in vitro and in vivo. In calcium mobilization studies CHO cells expressing the human NK receptors responded to a panel of agonists with the expected order of potency. In CHO NK(1) cells Netupitant concentration-dependently antagonized the stimulatory effects of substance P (SP) showing insurmountable antagonism (pK(B) 8.

The antiemetic 5-HT3 receptor antagonist Palonosetron inhibits substance P-mediated responses in vitro and in vivo.

Palonosetron is the only 5-HT(3) receptor antagonist approved for the treatment of delayed chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic chemotherapy. Accumulating evidence suggests that substance P (SP), the endogenous ligand acting preferentially on neurokinin-1 (NK-1) receptors, not serotonin (5-HT), is the dominant mediator of delayed emesis. However, palonosetron does not bind to the NK-1 receptor.

Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function.

Palonosetron is a 5-HT(3) receptor antagonist that has demonstrated superiority in preventing both acute and delayed emesis when compared to older first generation 5-HT(3) receptor antagonists. The objective of this work was to determine if palonosetron exhibits unique molecular interactions with the 5-HT(3) receptor that could provide a scientific rationale for observed clinical efficacy differences. Previously, we showed that palonosetron exhibits allosteric binding and positive cooperativity to the 5-HT(3) receptor in contrast to ondansetron and granisetron which exhibit simple bimolecular binding.

Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor.

Background: Palonosetron is a 5-HT(3)-receptor antagonist (5-HT(3)-RA) that has been shown to be superior to other 5-HT(3)-RAs in phase III clinical trials for the prevention of acute, delayed, and overall chemotherapy-induced nausea and vomiting. The improved clinical efficacy of palonosetron may be due, in part, to its more potent binding and longer half-life. However, these attributes alone are not sufficient to explain the results with palonosetron.