MP-157

Whereas Spinifex has focused on blocking the AT2 receptor, other developers are trying to stimulate it with AT2 agonists.The number of AT2 receptors increases after ttraumas such as heart attack or stroke in the damaged tissue, and the receptor appears to have a role in tissue repair.For example, Lanthio Pharma, a Netherlands-based company, published a paper last year showing that its AT2 agonist, LP2-3, provides some protection against lung injury in a mouse model of neonatal chronic lung disease.And Vicore Pharma, a drug company based in Gothenburg, Sweden, demonstrated that its agonist, called Compound 21 (C21), can improve recovery in rats following spinal cord injury.As a first step, however, Vicore will probably focus on pulmonary fibrosis, a disease in which the lungs become increasingly scarred. "We′re a small company," says Per Jansson, managing director of Vicore. "That limits us." Because pulmonary fibrosis is such a serious disease, the trials will probably be shorter and less costly.Vicore is collaborating with University College London to conduct a phase 1 trial that is slated to begin this fall.Meanwhile, some researchers have revisited the idea that the AT2 receptor can be targeted to treat hypertension.The Japanese company Mitsubishi Tanabe Pharma, based in Osaka, has developed an agonist called MP-157.This compound is currently being tested in a phase 1 trial in Europe for hypertension.Whether an AT2 agonist could have any impact on hypertension remains to be seen, though.Unger′s research shows that AT2 agonists like C21 can cause dilation of blood vessels, but that effect doesn′t seem to translate into lower blood pressure.However, Lucinda Hilliard, a researcher at Monash University near Melbourne, points out that all the research on AT2 and hypertension has been done in male animals. "Females have a lot more of the AT2 receptor," she says.So Hilliard and her colleagues are investigating in preclin. studies whether females will respond differently.And although AT2 agonists may not lower blood pressure on their own, they do seem to have an effect when AT1 is blocked.So it′s possible they could work well in concert with other hypertension drugs, she says.AT2 is "still a mysterious receptor, sometimes exerting beneficial effects and sometimes exerting bad effects," says Jan Danser, a pharmacologist who studies AT2 at the Erasmus University Medical Center in Rotterdam, the Netherlands. "That makes it very complicated as a drug target," he adds. "We don′t even know whether we should block it or stimulate it.