Rovatirelin Hydrate(Rovatirelin Hydrate) - 药物靶点：TRHR_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Rovatirelin、Rovatirelin hydrate (JAN)、Rovatirelin trihydrate

+ [3]

靶点

TRHR

作用机制

TRHR激动剂(促甲状腺素释放激素受体激动剂)

治疗领域

神经系统疾病遗传病与畸形其他疾病+ [2]

在研适应症-

非在研适应症

帕金森病半规管裂综合征脊髓小脑性共济失调

原研机构

Shionogi & Co., Ltd.

在研机构-

非在研机构

Shionogi & Co., Ltd.

Kissei Pharmaceutical Co., Ltd.

最高研发阶段终止申请上市

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (欧盟)

登录后查看时间轴

结构

分子式C16H22N4O4S

InChIKeyWTXWDXWZGJGIHV-URBCHYCLSA-N

CAS号204386-76-5

查看全部结构式(2)

关联

8

项与 Rovatirelin Hydrate 相关的临床试验

NCT01384435 / Completed临床2期

A Randomized, Double Blind, Placebo-controlled Phase II Study of KPS-0373 in Patients With SCD

The purpose of this study is to evaluate the efficacy and safety of KPS-0373 compared to placebo in patients with Spinocerebellar Degeneration (SCD).

开始日期-

申办/合作机构

Kissei Pharmaceutical Co., Ltd.

NCT02889302 / Completed临床3期

An Additional Phase III Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)

The purpose of this study is to investigate the superiority of KPS-0373 to placebo, and evaluate the safety of KPS-0373 in SCD patients.

开始日期2016-11-15

申办/合作机构

Kissei Pharmaceutical Co., Ltd.

NCT01970098 / Completed临床3期

A Phase III Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)

The purpose of this study is to investigate the superiority of KPS-0373 to placebo, and evaluate the safety and pharmacokinetics of KPS-0373 in SCD patients.

开始日期2013-10-09

申办/合作机构

Kissei Pharmaceutical Co., Ltd.

100 项与 Rovatirelin Hydrate 相关的临床结果

登录后查看更多信息

100 项与 Rovatirelin Hydrate 相关的转化医学

登录后查看更多信息

100 项与 Rovatirelin Hydrate 相关的专利（医药）

登录后查看更多信息

1,307

项与 Rovatirelin Hydrate 相关的文献（医药）

2024-12-01·Clinical Biochemistry

Multidisciplinary approach to redefining thyroid hormone reference intervals with big data analysis

Article

作者: Kline, Gregory ; Gifford, Jessica L ; Raizman, Joshua E ; Lewis, Cody W. ; Higgins, Victoria ; Raizman, Joshua E. ; Huang, Carol ; Symonds, Christopher ; Venner, Allison A. ; Venner, Allison A ; Lewis, Cody W ; Romney, Jacques ; Gifford, Jessica L. ; Doulla, Manpreet

OBJECTIVESThis study aimed to employ big data analysis to harmonize reference intervals (RI) for thyroid function tests, with refinement to the TSH upper reference limit, and to optimize the TSH reflex algorithm to improve clinical management and test utilization.DESIGN & METHODSTSH, free T4, and free T3 results tested in Alberta, Canada, on Roche Cobas and Siemens Atellica were extracted from the laboratory information system (N = 1,144,155 for TSH, N = 183,354 for free T4 and N = 92,632 for free T3). Results from specialists, inpatients, or repeat testing, as well as from positive thyroid disease, autoimmune disease, and pregnancy biomarkers were excluded. RIs were derived using statistical models (Bhattacharya, refineR, and simple non-parametric) followed by endocrinology and laboratory review.RESULTSThe TSH RIs for 0 to 7 days, 8 days to 1 year, and ≥1 year were 1.23 to 25.0 mIU/L, 1.00 to 6.80 mIU/L and 0.20 to 6.50 mIU/L, respectively. The free T4 RIs for 0 to 14 days, 15 to 29 days, and ≥30 days were 13.5 to 50.0 pmol/L, 8.7 to 32.5 pmol/L, and 10.0 to 25.0 pmol/L, respectively. An updated TSH reflex algorithm was developed based on the optimized TSH and free T4 RIs, with free T4 reflexed only at a TSH of <0.1 mIU/L.CONCLUSIONSThe collaboration of a multidisciplinary team and the utilization of big data analysis led to the enhancement of thyroid function RIs, specifically resulting in the widening of the upper TSH reference limit to 6.50. Application of these optimized RIs with the TSH reflex algorithm will serve as a guide for improvement in interpretation of thyroid function tests.

2024-12-01·Hormones

Effect of TSH on aromatase expression of ovarian granulosa cells in obese mice

Article

作者: Zhu, Liping ; Ma, Ling ; Zhou, Xinhui ; Hu, Yanyan

PURPOSEAromatase plays an important role in ovarian development, the normal progress of the menstrual cycle, and fertility status. Elevated aromatase activity is linked to obesity. There is a bidirectional relationship between obesity and thyroid function. Few studies have investigated the relationship between TSH and ovarian aromatase in obesity. Our aim was to investigate the effect of TSH on aromatase expression of ovarian granulosa cells in obese mice.METHODSFemale mice pups were divided into an obesity group and a control group. Obese parameters and the time of pubertal onset were recorded. At the age of 5 weeks, blood and tissues were obtained. Serum aromatase and hormone concentrations were measured using ELISA. The granulosa cells were isolated and exposed to variable concentrations (0 μM, 1 μM, 10 μM, 100 μM) of TSH. The expression of CYP19A1 mRNA and protein were assessed via RT-qPCR and western blot.RESULTSIn female mice, body weight, Lee's obesity index, and serum levels of E2, aromatase, and TSH were significantly higher in the obesity group compared to the control group, whereas the time of pubertal onset and serum T3 and T4 concentrations were significantly lower (all P < 0.001). In granulosa cells, the expression of CYP19A1 mRNA in the obesity group was lower than that in the control group at 1 μM and 100 μM concentrations of TSH (both P < 0.001). The expression of CYP19A1 protein in the obesity group was higher than that in the control group after TSH stimulation (P = 0.014, P < 0.001, and P = 0.004, respectively). With the increase of TSH concentrations, the expression of CYP19A1 mRNA and protein in the two groups significantly increased (all P < 0.001).CONCLUSIONEarly puberty and elevated serum aromatase and TSH levels were found in obese female mice. In the granulosa cells of obese mice, TSH directly regulates aromatase expression in a dose-dependent manner.

2024-12-01·Sleep Medicine

Impact of sleep restriction on biomarkers of thyroid function: Two pooled randomized trials

Article

作者: Cheng, Bin ; Petrov, Megan E. ; St-Onge, Marie-Pierre ; Jelic, Sanja ; Zuraikat, Faris M ; Aggarwal, Brooke ; Laferrère, Blandine ; Zuraikat, Faris M. ; Petrov, Megan E

BACKGROUNDChronic, mildly insufficient sleep is associated with increased cardiometabolic risk, but whether the regulation of thyroid hormones and related growth factors are mechanisms of this association is unclear. We investigated whether 6 wk of mild sleep restriction (SR) alters levels of free thyroxine (FT4), thyroid stimulating hormone (TSH), and fibroblast growth factor-21 (FGF-21), a modulator of FT4, in adults with adequate habitual sleep (AS; 7-9 h/night).METHODSHealthy adults participated in one of two randomized, crossover studies with identical 6-wk intervention phases: AS and SR (1.5 h/night < AS). Fasted blood samples were collected at baseline and endpoint of each phase. Outcomes were concentrations of FT4, TSH, and FGF-21 (women only). Linear mixed models tested the effects of SR vs AS on the outcomes, adjusting for baseline levels, week, sex, and sex-by-condition interaction.RESULTSThirty participants (20 women; 73% racial/ethnic minority; age 21-64 y [M±SD = 36.2 ± 12.8 y]) were included. In the full sample, no effects of SR on FT4 (β±SE = 0.02 ± 0.04, p = 0.654) or TSH (β±SE = -0.02 ± 0.04, p = 0.650) were observed; however, there were sex-by-condition interactions for both FT4 (p-interaction = 0.056) and TSH (p-interaction = 0.049). In sex-stratified analyses, TSH was reduced in SR vs. AS in women (β±SE = -0.11 ± 0.04, p = 0.011, Cohen's f² = 0.55) but not men (β±SE = 0.09 ± 0.08, p = 0.261). Among women (n = 17), FGF-21 was not significantly different between conditions (β±SE = 8.51 ± 17.70, p = 0.638).CONCLUSIONProlonged mild SR reduces TSH in women, whereas FT4 and FGF-21 remain unaffected compared with AS. If sustained, disruptions to the thyrotropic axis in women may contribute to their more pronounced cardiometabolic risk in response to SR compared with men.

100 项与 Rovatirelin Hydrate 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D10594	-	-	DB15338

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
脊髓小脑性共济失调	申请上市	日本	Kissei Pharmaceutical Co., Ltd.	2021-12-22
半规管裂综合征	申请上市	日本	Kissei Pharmaceutical Co., Ltd.	2009-03-18
帕金森病	申请上市	日本	Shionogi & Co., Ltd.	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02889302 \| NCT01970098 (Pubmed \| J Neurol Neurosurg Psychiatry)	临床3期	小脑共济失调	-	rovatirelin 2.4 mg	(製網觸鹽膚壓齋鑰艱齋): adjusted mean change = -0.61 (95% CI, -1.16 ~ -0.06), P-Value = 0.029	-	2020-03-01
				placebo