Elocalcitol, a vitamin D3 analog for the potential treatment of benign prostatic hyperplasia, overactive bladder and male infertility

被引:0
|
作者
Tiwari, Atul [1 ]
机构
[1] Jubilant Biosys Ltd, Drug Discovery Unit, Bangalore 560022, Karnataka, India
关键词
OXIDATIVE STRESS; PROINFLAMMATORY CYTOKINES; URINARY-INCONTINENCE; HORMONAL TREATMENT; RHOA/RHO-KINASE; BXL-628; THERAPY; RAT; RO-26-9228; MANAGEMENT;
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Elocalcitol, which had been under development by BioXell SpA, is a synthetic derivative of vitamin D 3 that regulates cell proliferation and apoptosis via its binding to the vitamin D receptor. In preclinical studies, elocalcitol inhibited the androgen-dependent and androgen-independent proliferation of benign prostatic hyperplasia (BPH) cells more potently than finasteride, a 5 alpha-reductase inhibitor. In a phase IIb trial in patients with BPH, treatment with elocalcitol resulted in a significantly reduced prostate volume compared with placebo; irritative urinary symptoms (frequency, urgency and nocturia) and urodynamic parameters were comparable to the alpha(1)-adrenoceptor antagonist tamsulosin. In a phase IIa trial in patients with prostatitis, elocalcitol significantly reduced levels of IL-8 in semen, suggesting improved quality and forward motility of sperm. However, phase IIb trial data from patients with overactive bladder (OAB) were less promising: elocalcitol failed to meet the primary endpoint despite demonstrating good efficacy in a phase IIa trial. Based largely on these disappointing data, BioXell decided to terminate all further clinical development of elocalcitol, including an uncompleted phase IIa trial in patients with male infertility. Given the novel mechanism of action, efficacy profile and improved tolerability of elocalcitol over existing classes of drugs, the compound could have potentially added to the armamentarium in the expanding therapeutic markets of BPH, OAB and male infertility. This possibility appears to have been negated by BioXell's recent decision to terminate all further development of elocalcitol.
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页码:381 / 393
页数:13
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