MT-1207(MT-1207) - 药物靶点：5-HT2A receptor_在研适应症：原发性高血压，前列腺增生症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

5-HT2A receptor

作用机制

5-HT2A receptor拮抗剂(5-羟色胺2A受体拮抗剂)

治疗领域

心血管疾病泌尿生殖系统疾病

在研适应症

原发性高血压前列腺增生症

非在研适应症-

原研机构

辽宁格林生物药业集团股份有限公司

在研机构

原研药港生命科学研究（辽宁）有限公司

辽宁格林生物药业集团股份有限公司

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)临床2期

特殊审评-

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结构

分子式C21H25ClN6S

InChIKeyUFMLXCNESJKXFY-UHFFFAOYSA-N

CAS号1610794-70-1

关联

6

项与 MT-1207 相关的临床试验

CTR20220993 / Completed临床2期

MT-1207片治疗轻、中度原发性高血压的有效性和安全性的随机、双盲、安慰剂和阳性药物平行对照、多中心II期临床试验

开始日期2022-05-29

申办/合作机构

辽宁格林生物药业集团股份有限公司

[+1]

ChiCTR2200060328 / Suspended临床2期IIT

Efficacy and safety of MT-1207 tablets in the treatment of mild and moderate essential hypertension: a randomized, double-blind, placebo-controlled, multicenter phase II clinical trial

开始日期2022-05-27

申办/合作机构-

CTR20201993 / Completed临床1期

评价 MT-1207 在高血压患者中单中心、随机、剂量递增、安慰剂和阳性对照的单次、多次给药的耐受性、药代动力学及药效学的Ⅰb期临床试验

主要目的：评价 MT-1207 在高血压患者中多剂量、单次、多次给药耐受性；评价 MT-1207 在高血压患者中多剂量、单次、多次给药药代动力学；次要目的：初步评价药效学

开始日期2020-11-20

申办/合作机构

辽宁格林生物药业集团股份有限公司

[+1]

100 项与 MT-1207 相关的临床结果

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100 项与 MT-1207 相关的转化医学

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100 项与 MT-1207 相关的专利（医药）

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6

项与 MT-1207 相关的文献（医药）

2024-09-26·Journal of Medicinal Chemistry

Discovery of MT-1207: A Novel, Potent Multitarget Inhibitor as a Promising Clinical Candidate for the Treatment of Hypertension

Article

作者: Zhu, Zheying ; Liu, Jie ; Tian, Jia-Sheng ; Zhu, Wenjian ; Xu, Shengtao ; Yao, Hong ; Xu, Jinyi ; Miao, Chao-Yu ; Zhu, Huajian ; Wang, Peng

Herein, a series of novel arylpiperazine (piperidine) derivatives were designed, synthesized, and evaluated for mechanisms of action through in vitro and in vivo studies. The most promising compound, II-13 (later named as MT-1207), is a potent α₁ and 5-HT_2A receptor antagonist with remarkable IC₅₀ in the picomolar level. Importantly, in the in vivo assay, II-13 achieved an effective blood pressure (BP) reduction in the 2K2C rat model without damaging renal function. Compound II-13, with its significant advantages in terms of pharmacological effects, pharmacokinetic parameters, and a large safety window, was extensively investigated. Moreover, data also showed that compound II-13 had fewer side effects in a postural BP assay and could prevent the onset of postural hypotension. Together, these results suggested that compound II-13 is a highly potent antihypertensive drug candidate with multitarget mechanisms of action in preclinical models. Currently, MT-1207 is in phase II hypertensive clinical trials in China.

2024-09-01·Biomedicine & Pharmacotherapy

Pharmacological effects of MT-1207 in bilateral renal artery stenosis hypertension and its hypotensive targets validation

Article

作者: Wang, Zhi ; Wei, Yu-Chen ; Tian, Jia-Sheng ; Miao, Zhu-Wei ; Ling, Qi-Sheng ; Miao, Chao-Yu ; Wang, Dao-Xin ; Wang, Peng

MT-1207 (MT) as a new antihypertensive drug is under clinical trial. However, its hypotensive mechanism has not been experimentally explored, and it is unknown whether MT can be used for bilateral renal artery stenosis hypertension. Using two-kidney two-clip (2K2C) to mimic bilateral renal artery stenosis in rats, a stroke-prone renovascular hypertension model, the present study further verified its antihypertensive effect, cardiovascular and renal protection, mortality reduction and lifespan prolongation, as well as demonstrated its two novel pharmacological effects for uric acid-lowering and cognition-improving. Notably, MT did not aggravate renal dysfunction; instead, it had beneficial effects on reducing serum uric acid level and maintaining serum K⁺ at a relatively stable level in 2K2C rats. In contrast, angiotensin receptor blocker losartan aggravated renal dysfunction in 2K2C rats. Mechanistically, MT hypotensive effect was dependent on its blockade of α₁ and 5-HT₂ receptors, since MT pretreatment abolished these receptor agonists-induced blood pressure elevations in vivo. Further evidence showed MT bound to and interacted with these receptor subtypes including α_1A, α_1B, α_1D, 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors known for control of blood pressure. In conclusion, MT may be used for treatment of bilateral renal artery stenosis hypertension, different from losartan that is prohibited for treatment of bilateral renal artery stenosis hypertension. Targets validation of MT hypotensive mechanism and beneficial effects of MT on uric acid and cognitive function provide new insights for this novel multitarget drug, deserving clinical trial attention.

2023-10-01·Pharmaceutical development and technology

Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers.

Article

作者: Roberts, Clive J ; Wang, Yuhan ; Vrettos, Napoleon-Nikolaos ; Wang, Peng ; Xu, Jinyi ; Zhu, Zheying ; Yao, Hong

In the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers, namely polyethylene oxide and Kollidon^® SR. A factorial experiment was conducted, and the results revealed a non-effervescent gastroretentive layer that, unlike most gastroretentive layers reported in the literature, was easy to prepare, and provided immediate tablet buoyancy (mean floating lag time of 1.5 s) that lasted over 24 h in fasted state simulated gastric fluid (FaSSGF) pH 1.6, irrespective of the drug layer, thereby allowing a 24-hour sustained release of MT-1207 from the drug layer of the tablets. Furthermore, during in vitro buoyancy testing of the optimised bilayer tablets in media of different pH values (1.0, 3.0, 6.0), the significant difference (one-way ANOVA, p < 0.001) between the respective total floating times indicated that stomach pH effects on tablet buoyancy are important to be considered during the development of non-effervescent gastroretentive formulations and the choice of dosing regimen. To the best of our knowledge, this has not been reported before, and it should probably be factored in when designing dosing regimens. Finally, a pharmacokinetic study in Beagle dogs indicated a successful in vivo 24-hour sustained release of MT-1207 from the optimised gastroretentive bilayer tablet formulations with the drug plasma concentration remaining above the estimated minimum effective concentration of 1 ng/mL at the 24-hour timepoint and also demonstrated the gastroretentive capabilities of the hydrophilic and hydrophobic polymer combination. The optimised formulations will be forwarded to clinical development.

100 项与 MT-1207 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
原发性高血压	临床2期	中国	辽宁格林生物药业集团股份有限公司	2022-05-29
原发性高血压	临床2期	中国	原研药港生命科学研究（辽宁）有限公司	2022-05-29
前列腺增生症	临床申请批准	中国	原研药港生命科学研究（辽宁）有限公司	2024-04-28