Sovesudil(Sovesudil) - 药物靶点：ROCK_在研适应症：青光眼_专利_临床

概要

基本信息

药物类型

小分子化药

别名

AMA0076

+ [1]

靶点

ROCK

作用机制

ROCK 抑制剂(Rho-相关激酶抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Katholieke Universiteit Leuven

非在研机构

pH Pharma Co., Ltd.初创企业

Amakem NV

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/序列

分子式C23H22FN3O3

InChIKeyPNWBYIFLWUCWKS-UHFFFAOYSA-N

CAS号1333400-14-8

关联

6

项与 Sovesudil 相关的临床试验

NCT04863365

/ Unknown status临床3期

A Multi-center, Randomized, Placebo-controlled, Double-blind, Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of PHP-201 in Patients With Primary Open-angle Glaucoma or Ocular Hypertension

This is a phase 3 study to confirm the efficacy in reduction of intraocular pressure and safety of PHP-201 ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension.

开始日期2021-11-01

申办/合作机构

pH Pharma Co., Ltd.初创企业

NCT03586908

/ Completed临床1期

An Open Label, Multiple-dose, Phase 1 Clinical Trial to Evaluate Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of PHP-201 Topical Eye Drop in Korean and Japanese Healthy Subjects

An open label, multiple-dose, phase 1 clinical trial to evaluate pharmacokinetics, pharmacodynamics, safety and tolerability of PHP-201 topical eye drop in Korean and Japanese healthy subjects

开始日期2018-02-04

申办/合作机构

pH Pharma Co., Ltd.初创企业

NCT03106532

/ Completed临床2期

A Multicenter, Randomized, Placebo-controlled, Double-blind, Dose-finding Phase 2 Clinical Trial to Evaluate the Efficacy in Reduction of Intraocular Pressure and Safety of PHP-201 in Patients With Normal Tension Glaucoma

Evaluation of the optimal dose for the efficacy in reduction of intraocular pressure and safety of PHP-201 ophthalmic solution in patients with normal tension glaucoma

开始日期2017-03-06

申办/合作机构

pH Pharma Co., Ltd.初创企业

100 项与 Sovesudil 相关的临床结果

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100 项与 Sovesudil 相关的转化医学

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100 项与 Sovesudil 相关的专利（医药）

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6

项与 Sovesudil 相关的文献（医药）

2023-07-01·Experimental Eye Research

Identifying new drugs and targets to treat rapidly elevated intraocular pressure for angle closure and secondary glaucomas to curb visual impairment and prevent blindness

Review

作者: Sharif, Najam A

A multitude of pharmacological compounds have been shown to lower and control intraocular pressure (IOP) in numerous species of animals and human subjects after topical ocular dosing or via other routes of administration. Most researchers have been interested in finding drug candidates that exhibit a relatively long duration of action from a chronic therapeutic use perspective, for example to treat ocular hypertension (OHT), primary open-angle glaucoma and even normotensive glaucoma. However, it is equally important to seek and characterize treatment modalities which offer a rapid onset of action to help provide fast relief from quickly rising IOP that occurs in certain eye diseases. These include acute angle-closure glaucoma, primary angle-closure glaucoma, uveitic and inflammatory glaucoma, medication-induced OHT, and other secondary glaucomas induced by eye injury or infection which can cause partial or complete loss of eyesight. Such fast-acting agents can delay or prevent the need for ocular surgery which is often used to lower the dangerously raised IOP. This research survey was therefore directed at identifying agents from the literature that demonstrated ocular hypotensive activity, normalizing and unifying the data, determining their onset of action and rank ordering them on the basis of rapidity of action starting within 30-60 min and lasting up to at least 3-4 h post topical ocular dosing in different animal species. This research revealed a few health authority-approved drugs and some investigational compounds that appear to meet the necessary criteria of fast onset of action coupled with significant efficacy to reduce elevated IOP (by ≥ 20%, preferably by >30%). However, translation of the novel animal-based findings to the human conditions remains to be demonstrated but represent viable targets, especially EP₂-receptor agonists (e.g. omidenepag isopropyl; AL-6598; butaprost), mixed activity serotonin/dopamine receptor agonists (e.g. cabergoline), rho kinase inhibitors (e.g. AMA0076, Y39983), CACNA2D1-gene product inhibitors (e.g. pregabalin), melatonin receptor agonists, and certain K⁺-channel openers (e.g. nicorandil, pinacidil). Other drug candidates and targets were also identified and will be discussed.

2022-03-01·Acta Ophthalmologica3区 · 医学

Sovesudil (locally acting rho kinase inhibitor) for the treatment of normal‐tension glaucoma: the randomized phase II study

3区 · 医学

Article

作者: Park, Ki Ho ; Satyal, Sanjeev ; Kim, Jaesoon ; Kim, Soojin ; Kim, Young Kook ; Jeoung, Jin Wook ; Ha, Ahnul

AbstractPurposeTo evaluate ocular hypotensive efficacy and the safety of sovesudil (formally known as PHP‐201), a novel Rho‐associated protein kinase (ROCK) inhibitor, in patients with normal‐tension glaucoma (NTG).DesignMulticentre, prospective, double‐masked, randomized, placebo‐controlled, parallel clinical study.MethodsPatients with NTG (unmedicated baseline IOP ≤ 21 mmHg) were randomized in 3 groups and treated with sovesudil in concentrations of 0.25% and 0.5%, or with a placebo three times daily (TID) for 4 weeks. The primary end‐point was the mean diurnal IOP change from the baseline at week 4. Safety was recorded over a 4‐week treatment period and the following 2‐week observation period.ResultsA total of 119 patients were included in the primary efficacy analysis. The mean diurnal IOP change from the baseline at week 4 was −1.56 mmHg for the high‐dose group, −1.10 mmHg for the low‐dose group and −0.65 mmHg for the placebo group. The difference between the high‐dose and the placebo groups was −0.91 mmHg (95% confidence intervals: −1.73, −0.09). 0.5% sovesudil TID met the criteria for superiority to the placebo. The most frequent ocular adverse event among sovesudil‐treated patients was conjunctival hyperaemia (24.4% for the high‐dose and 17.5% for the low‐dose group) and predominately classified as mild.ConclusionsSovesudil 0.25% and 0.5% TID showed statistically significant IOP‐lowering effects and 0.5% concentration’s IOP‐lowering effects met the superiority criteria in comparison with the placebo at week 4. Sovesudil was well tolerated with mild adverse events including relatively low incidence of conjunctival hyperaemia in patients with NTG.

2020-04-29·Current Medicinal Chemistry2区 · 医学

Rho-kinase (ROCK) Inhibitors - A Neuroprotective Therapeutic Paradigm with a Focus on Ocular Utility

2区 · 医学

Review

作者: Piplani, Poonam ; Abbhi, Vasudha

Background:Glaucoma is a progressive optic neuropathy causing visual impairment and Retinal Ganglionic Cells (RGCs) death gradually posing a need for neuroprotective strategies to minimize the loss of RGCs and visual field. It is recognized as a multifactorial disease, Intraocular Pressure (IOP) being the foremost risk factor. ROCK inhibitors have been probed for various possible indications, such as myocardial ischemia, hypertension, kidney diseases. Their role in neuroprotection and neuronal regeneration has been suggested to be of value in the treatment of neurological diseases, like spinal-cord injury, Alzheimer’s disease and multiple sclerosis but recently Rho-associated Kinase inhibitors have been recognized as potential antiglaucoma agents.Evidence Synthesis:Rho-Kinase is a serine/threonine kinase with a kinase domain which is constitutively active and is involved in the regulation of smooth muscle contraction and stress fibre formation. Two isoforms of Rho-Kinase, ROCK-I (ROCK β) and ROCK-II (ROCK α) have been identified. ROCK II plays a pathophysiological role in glaucoma and hence the inhibitors of ROCK may be beneficial to ameliorate the vision loss. These inhibitors decrease the intraocular pressure in the glaucomatous eye by increasing the aqueous humour outflow through the trabecular meshwork pathway. They also act as anti-scarring agents and hence prevent post-operative scarring after the glaucoma filtration surgery. Their major role involves axon regeneration by increasing the optic nerve blood flow which may be useful in treating the damaged optic neurons. These drugs act directly on the neurons in the central visual pathway, interrupting the RGC apoptosis and therefore serve as a novel pharmacological approach for glaucoma neuroprotection.Conclusion:Based on the results of high-throughput screening, several Rho kinase inhibitors have been designed and developed comprising of diverse scaffolds exhibiting Rho kinase inhibitory activity from micromolar to subnanomolar ranges. This diversity in the scaffolds with inhibitory potential against the kinase and their SAR development will be intricated in the present review. Ripasudil is the only Rho kinase inhibitor marketed to date for the treatment of glaucoma. Another ROCK inhibitor AR-13324 has recently passed the clinical trials whereas AMA0076, K115, PG324, Y39983 and RKI-983 are still under trials. In view of this, a detailed and updated account of ROCK II inhibitors as the next generation therapeutic agents for glaucoma will be discussed in this review.

100 项与 Sovesudil 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
开角型青光眼	临床2期	韩国	pH Pharma Co., Ltd.初创企业	2021-11-01
低眼压性青光眼	临床2期	韩国	pH Pharma Co., Ltd.初创企业	2017-03-06
青光眼	临床2期	英国	Amakem NV	2013-09-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


PHP-201 (APAO2019)	临床2期	青光眼	119	PHP-201 0.25%	製範憲餘積遞膚餘壓範(襯積膚積衊鏇艱鹽觸願) = 1 (2.63%) of 38 patients for the placebo group, 7 (17.5%) of 40 patients for 0.25% group, and 10 (24.4%) of 41 patients for 0.5% group 鬱鹹簾鹽製淵鹹遞製鏇 (鬱製獵積憲鏇鑰鏇艱觸 )	积极	2019-03-06
				PHP-201 0.5%
ARVO2013	N/A	-	5	AMA0076	(淵構簾廠構遞簾選積蓋) = Hyperemia was observed with all concentrations of Y-39983 whereas only mild hyperemia was induced after administration of AMA0076 0.4% (highest concentration used) 襯簾廠淵願鏇鬱鏇蓋艱 (遞鑰獵範齋顧膚觸蓋廠 )	-	2013-06-01
				Y-39983
ARVO2012	N/A	低眼压	-	AMA0076 0.1% + 0.01% BAK	(積網鬱鑰膚製繭網選鹹) = 積艱衊網餘膚糧衊觸夢製網製製網膚顧繭蓋餘 (淵憲製範簾構鑰憲遞襯 )	积极	2012-03-01
				AMA0076 0.3% + 0.01% BAK	(積網鬱鑰膚製繭網選鹹) = 衊鑰廠餘壓鏇廠築觸衊製網製製網膚顧繭蓋餘 (淵憲製範簾構鑰憲遞襯 )