ONO-7300243 is a novel, potent LPA1 antagonist (LPA1: IC50 = 160 nM, LPA induced rat IUP model ID50 =11.6 mg/kg p.o.). ONO-7300243 showed good efficacy in vivo. The oral dosing of ONO-7300243 at 30 mg/kg led to reduced intraurethral pressure in rats. Notably, ONO-7300243 was equal in potency to the α1 adrenoceptor antagonist tamsulosin, which is used in clinical practice to treat dysuria with benign prostatic hyperplasia (BPH). In contrast to tamsulosin, ONO-7300243 had no impact on the mean blood pressure at this dose. These results suggest that LPA1 antagonists could be used to treat BPH without affecting the blood pressure. Lysophosphatidic acid (LPA) evokes various physiological responses through a series of G protein-coupled receptors known as LPA1−6.
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