Elocalcitol(Elocalcitol) - 药物靶点：VDR_在研适应症：成骨不全，Rett综合征_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

VDR

作用机制

VDR激动剂(维生素D受体激动剂)

治疗领域

神经系统疾病遗传病与畸形皮肤和肌肉骨骼疾病+ [1]

在研适应症

成骨不全Rett综合征

非在研适应症

男性不育症绝经期后骨质疏松前列腺增生症+ [2]

原研机构

Roche Palo Alto LLC

在研机构

Adge Pharmaceuticals Inc.

非在研机构

F. Hoffmann-La Roche Ltd.

BioXell SpA

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C29H43FO2

InChIKeyLRLWXBHFPGSUOX-GJQYOBCGSA-N

CAS号199798-84-0

关联

5

项与 Elocalcitol 相关的临床试验

EUCTR2007-001214-16-LT / Not yet recruitingN/A

A randomized, double blind, placebo controlled,parallel-group, multi-centre, Phase IIb, study to determine the effect of BXL628 in women with detrusor overactivity - BXL628 effect in OAB

开始日期2008-06-17

申办/合作机构

BioXell SpA

EUCTR2007-002859-16-IT / Not yet recruitingN/A

A randomized, double blind, placebo controlled, parallel group study to determine the effect of Elocalcitol on sperm parameters in infertile male patients - ND

开始日期2007-10-10

申办/合作机构

BioXell SpA

EUCTR2005-000154-76-DE / Not yet recruitingN/A

A randomized, double blind, double dummy, placebo controlled, parallel group study to determine the effect of BXL628 in monotherapy (75 mcg and 150 mcg) and in combination (150 mcg) with tamsulosin (0.4 mg) in patients with benign prostatic hyperplasia (BPH)

开始日期2006-08-28

申办/合作机构-

100 项与 Elocalcitol 相关的临床结果

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100 项与 Elocalcitol 相关的转化医学

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100 项与 Elocalcitol 相关的专利（医药）

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37

项与 Elocalcitol 相关的文献（医药）

2019-08-01·Journal of Endocrinological Investigation2区 · 医学

Comparative study of testosterone and vitamin D analogue, elocalcitol, on insulin-controlled signal transduction pathway regulation in human skeletal muscle cells

2区 · 医学

Article

作者: Lenzi, A ; Marampon, F ; Di Luigi, L ; Tombolini, V ; Crescioli, C ; Antinozzi, C ; Sgrò, P

PURPOSESkeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects.AIMTo elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets.METHODSHuman fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression.RESULTST, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression.CONCLUSIONSAll together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.

2017-05-01·Experimental and Therapeutic Medicine4区 · 医学

1,25-(OH)2D3 and its analogue BXL-628 inhibit high glucose-induced activation of RhoA/ROCK pathway in HK-2 cells

4区 · 医学

Article

作者: Liu, Jishi ; Zhang, Wei ; Zhang, Hao ; Huang, Jing ; Yi, Bin ; Yang, Shikun ; Zhang, Ke ; Li, Aimei

It has previously been reported that 1,25-(OH)₂D₃ inhibits high glucose-induced epithelial-to-mesenchymal transition (EMT) in HK-2 cells. However, the mechanism of this renoprotective action remains unclear. Elocalcitol (BXL-628), a vitamin D analog, has been suggested to be effective on the RhoA/Rho associated protein kinase (ROCK) pathway, which serves a crucial role in high glucose-induced EMT. The aim of the present study was to investigate the effect of 1,25-(OH)₂D₃ and its analogue BXL-628 on high glucose-induced activation of the RhoA/ROCK pathway in human renal proximal tubular cells. HK-2 cells were co-treated with high glucose and either 1,25-(OH)2D3 or BXL-628. The RhoA expression levels and ROCK activity of the membrane were assessed via western blot analysis or immunofluorescence. α-smooth muscle actin (α-SMA) and epithelial (E)-cadherin were detected using western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), whereas collagen I and fibronectin levels were measured by ELISA and RT-qPCR. The results demonstrated that 1,25-(OH)₂D₃ and BXL-628 both significantly downregulated the expression of active RhoA and ROCK activity induced by high glucose (P<0.05). Furthermore, the expressions of α-SMA, collagen I, and fibronectin were significantly downregulated at both protein and mRNA (P<0.05) levels, whereas the expression of E-cadherin was significantly increased (P<0.05) by 1,25-(OH)₂D₃ or BXL-628 treatment. In conclusion, the vitamin D receptor agonist 1,25-(OH)₂D₃ and its analogue BXL-628 were both able to attenuate high glucose-induced EMT and extracellular matrix accumulation of HK-2 cells by suppressing the RhoA/ROCK signaling pathway in vitro.

2017-03-01·The Journal of Steroid Biochemistry and Molecular Biology2区 · 生物学

Potential role for the VDR agonist elocalcitol in metabolic control: Evidences in human skeletal muscle cells

2区 · 生物学

Article

作者: Di Luigi, Luigi ; Riccieri, Valeria ; Valesini, Guido ; Minisola, Salvatore ; Crescioli, Clara ; Migliaccio, Silvia ; Pisano, Annalinda ; Giordano, Carla ; Cerbelli, Bruna ; Lenzi, Andrea ; Antinozzi, Cristina ; Corinaldesi, Clarissa ; Vannelli, Gabriella Barbara ; Stefanantoni, Katia

Vitamin D plays a pivotal role to maintain skeletal muscle integrity and health. Vitamin D deficiency characterizes inflammatory myopathy (IM) and diabetes, often overlapping diseases involving skeletal muscle damage. Vitamin D receptor (VDR) agonists likely exert beneficial effects in both IM and metabolic disturbances. We aim to evaluate in vitro the effect of elocalcitol, a non-hypercalcemic VDR agonist, on the biomolecular metabolic machinery of human skeletal muscle cells (Hfsmc), vs. insulin (I). We analyzed GLUT4, Flotillin-1, Caveolin-3 and Caveolin-1 cell expression/localization; mTOR, AKT, ERK and 4E-BP1 phosphorylation; IL-6 myokine release; VDR expression. We investigated in vivo vitamin D status in IM subjects, evaluating VDR muscular expression and serum vitamin D with metabolism-related parameters, as glycemia, triglycerides, cholesterol, resistin and adiponectin. In Hfsmc, elocalcitol exerted an I-like effect, promoting GLUT4 re-localization in Flotillin-1, Caveolin-3 and Caveolin-1 positive sites and mTOR, AKT, ERK, 4E-BP1 activation; it enhanced IL-6 myokine release. IM subjects, all normoglycemic, showed VDR/vitamin D deficiency that, together with high lipidemic and resistin profile, possibly increases the risk to develop metabolic diseases. VDR agonists as elocalcitol may be therapeutic tools for skeletal muscle integrity/function maintenance, an indispensable condition for health homeostasis.

100 项与 Elocalcitol 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06194

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
男性不育症	临床1期	-	F. Hoffmann-La Roche Ltd.	-
绝经期后骨质疏松	临床1期	美国	-	-
前列腺增生症	临床1期	-	F. Hoffmann-La Roche Ltd.	-
膀胱过度活动症	临床1期	-	F. Hoffmann-La Roche Ltd.	-
成骨不全	临床前	美国	Adge Pharmaceuticals Inc.	-
Rett综合征	临床前	美国	Adge Pharmaceuticals Inc.	-
男性不育症	药物发现	-	F. Hoffmann-La Roche Ltd.	-
前列腺增生症	药物发现	-	F. Hoffmann-La Roche Ltd.	-
前列腺炎	药物发现	-	F. Hoffmann-La Roche Ltd.	-
膀胱过度活动症	药物发现	-	F. Hoffmann-La Roche Ltd.	-