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Overview
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Background
IC50: 160 nM
ONO-7300243 is a LPA1 antagonist.
Lysophosphatidic acids (LPAs), a bioactive class of phospholipids, are produced by autotaxin from lysophosphatidylcholine in blood. LPAs have a wide range of cellular responses, such as cell proliferation, intracellular Ca2+ mobilization, cell survival, and cell motility. Based on their specific properties, LPAs have been involved in various complex physiological responses, such as the contraction of smooth muscle, wound healing, coagulation, demyelization, as well as immunological competence.
In vitro: ONO-7300243 was identified as a novel and potent LPA1 antagonist. Importantly, it was found that ONO-7300243 showed equal potency to the α1 adrenoceptor antagonist tamsulosin that is clinically used for the treatment of dysuria with benign prostatic hyperplasia (BPH) [1].
In vivo: Animal study reported that although ONO-7300243 showed only modest in vitro activity (IC50 = 0.16 μM), the oral dosing of ONO-7300243 to rats resulted in much stronger effects on reducing intraurethral pressure (88% inhibition at 10 mg/kg i.d., 62% inhibition at 3 mg/kg i.d.). When compared with tamsulosin, ONO-7300243 had no effect on the mean blood pressure at this dose, which suggested that LPA1 antagonists could be used to treat BPH without affecting the blood pressure [1].
Clinical trial: Up to now, ONO-7300243 is still in the preclinical development stage.
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- Properties
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Overview
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