H-1337(H-1337) - 药物靶点：LRRK2 x PKA x PKD1 x PKN2_在研适应症：开角型青光眼1A_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

LRRK2 x PKA x PKD1 x PKN2

作用方式

抑制剂

作用机制

LRRK2抑制剂(富含亮氨酸重复的丝氨酸/苏氨酸蛋白激酶-2抑制剂)、PKD1抑制剂(polycystin 1, transient receptor potential channel interacting inhibitors)、PKN2抑制剂(protein kinase N2 inhibitors)

+ [1]

治疗领域

眼部疾病

在研适应症

开角型青光眼1A

非在研适应症-

原研机构

D. Western Therapeutics Institute, Inc.

在研机构

D. Western Therapeutics Institute, Inc.

非在研机构

Allysta Pharmaceuticals, Inc.初创企业

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

3

项与 H-1337 相关的临床试验

NCT06572397

/ Completed临床1期

An Open-Label Study Assessing the Ocular and Systemic Safety and Systemic Absorption of H1337 Ophthalmic Solution, 1% in Healthy Volunteers

The trial will evaluate the safety of one dose regimen of H-1337 [1% twice daily (b.i.d.)] in both eyes in healthy volunteers.

开始日期2024-09-16

申办/合作机构

D. Western Therapeutics Institute, Inc.

NCT05913232

/ Completed临床2期

A Phase 2b Randomized, Double-masked, Active-controlled, Dose-response Study of the Safety and Efficacy of H-1337 in Subjects With Primary Open Angle Glaucoma (POAG) or Ocular Hypertension

The trial will evaluate the safety and efficacy of 3 dose regimens of H-1337 [0.6% twice daily (b.i.d.), 1.0% b.i.d. and 1.0% once in the morning (q.a.m.), and timolol maleate (0.5%, b.i.d.) in both eyes for 28 days.

开始日期2023-08-28

申办/合作机构

D. Western Therapeutics Institute, Inc.

NCT03452033

/ Completed临床1/2期

A Phase 1/2a Randomized, Double-masked, Placebo Controlled, Dose-ranging Study of the Safety and Efficacy of H-1337 in Subjects With Primary Open Angle Glaucoma (POAG) or Ocular Hypertension

The study will evaluate the safety, tolerability, and preliminary efficacy of three concentrations of H-1337 and vehicle administered twice daily in a parallel group, double-masked design for 28 days of dosing in patients with elevated intraocular pressure (IOP).

开始日期2018-03-15

申办/合作机构

Allysta Pharmaceuticals, Inc.初创企业

100 项与 H-1337 相关的临床结果

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100 项与 H-1337 相关的转化医学

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100 项与 H-1337 相关的专利（医药）

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4

项与 H-1337 相关的文献（医药）

2023-03-01·Ophthalmology Glaucoma

Phase Ⅰ/Ⅱ, Double-Masked, Randomized, Vehicle-Controlled Study of H-1337 Ophthalmic Solution for Glaucoma and Ocular Hypertension

Article

作者: Hidaka, Hiroyoshi ; Hartman, Paul J ; Novack, Gary D ; Cooke, David L ; Stewart, Jeanette ; Hsu, Henry H ; Yoshida, Yoko ; Sumi, Kengo

PURPOSETo perform a phase Ⅰ/Ⅱ evaluation of an H-1337 ophthalmic solution in subjects with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).DESIGNThis was a phase I/II, randomized, double-masked, vehicle-controlled, dose-response study conducted at 6 private practice sites in the United States. The study was registered with clinicaltrials.gov as NCT03452033.PARTICIPANTSEighty-seven subjects with bilateral POAG or OHT were enrolled.METHODSAfter washout of ocular hypotensive medications as required, the subjects were randomized to receive either the H-1337 ophthalmic solution at 0.06%, 0.2%, and 0.6% or its vehicle twice daily unilaterally in the study eye for the first 3 days and then twice daily in both eyes from day 4 to 28.MAIN OUTCOME MEASURESThe primary efficacy end point was the mean change in intraocular pressure from baseline (day 0) for each group on day 28 at hour 4 compared with the vehicle.RESULTSIn the primary efficacy end point, i.e., mean change from the baseline on day 28 at hour 4, the mean change from the baseline was - 4.45 ± 3.801, - 5.16 ± 3.114, - 4.93 ± 3.110, and - 0.39 ± 2.355 in the 0.06%, 0.2%, and 0.6% H-1337 and vehicle groups, respectively. The difference between each active group and the vehicle group was statistically significant (P < 0.0001). Treatment-emergent adverse events (TEAEs) occurred in 49% of subjects who received H-1337 (range, 41% [0.2% arm]-64% [0.6% arm] across the H-1337 arms) and 18% of subjects who received the vehicle. The majority of TEAEs were mild in severity; 3 subjects who received H-1337 had a TEAE of moderate intensity (instillation site erythema, blurred vision, and muscle strain).CONCLUSIONSThe H-1337 ophthalmic solution showed clinically and statistically significant ocular hypotensive activity and was well tolerated, with a relatively low incidence of hyperemia.FINANCIAL DISCLOSURE(S)Proprietary or commercial disclosure may be found after the references.

2008-01-01·Molekuliarnaia genetika, mikrobiologiia i virusologiia

[Difference in amino acid sequences of B. afzelii P66 surface-exposed loop region].

Article

作者: Korenberg, E I ; Morozov, A V ; Gorelova, N B ; Fadeeva, I A

In the present work, we performed a phenotyping analysis of 45 B. afzelii 89-a.a. long amino acid sequences of 7 different allele variants, corresponding to the surface-exposed loop region of P66. 45 investigated isolates showed 5 phenotypically different variants; 2 phenotypically different variants of loop region, in particular, also showed mutations in the putative monoclonal antibody H1337 binding site; the similarity between the amino acid sequences taken from different variants is about 96.66% to 98.88%; in one natural locus up to 3 different phenotypes of P66 could circulate simultaneously.

Cells3区 · 生物学

The Isoquinoline-Sulfonamide Compound H-1337 Attenuates SU5416/Hypoxia-Induced Pulmonary Arterial Hypertension in Rats

3区 · 生物学

ArticleOA

作者: Sanada, Takayuki Jujo ; Sakao, Seiichiro ; Hidaka, Hiroyoshi ; Tatsumi, Koichiro ; Sumi, Kengo ; Naito, Akira ; Maruyama, Junko ; Zhang, Erquan ; Yoshida, Yoko ; Maruyama, Kazuo ; Shoji, Hiroki

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure and right heart failure. Selective pulmonary vasodilators have improved the prognosis of PAH; however, they are not able to reverse pulmonary vascular remodeling. Therefore, a search for new treatment agents is required. H-1337 is an isoquinoline-sulfonamide compound that inhibits multiple serine/threonine kinases, including Rho-associated protein kinase (ROCK) and mammalian target of rapamycin (mTOR). Here, we investigated the effects of H-1337 on pulmonary hypertension and remodeling in the pulmonary vasculature and right ventricle in experimental PAH induced by SU5416 and hypoxia exposure. H-1337 and H-1337M1 exerted inhibitory effects on ROCK and Akt. H-1337 inhibited the phosphorylation of myosin light chain and mTOR and suppressed the proliferation of smooth muscle cells in vitro. H-1337 treatment also suppressed the phosphorylation of myosin light chain and mTOR in the pulmonary vasculature and decreased right ventricular systolic pressure and the extent of occlusive pulmonary vascular lesions. Furthermore, H-1337 suppressed aggravation of right ventricle hypertrophy. In conclusion, our data demonstrated that inhibition of ROCK and mTOR pathways with H-1337 suppressed the progression of pulmonary vascular remodeling, pulmonary hypertension, and right ventricular remodeling.

100 项与 H-1337 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1A	临床2期	美国	D. Western Therapeutics Institute, Inc.	2023-08-28
开角型青光眼	临床前	美国	Allysta Pharmaceuticals, Inc.初创企业	2018-03-15

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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


NCT03452033 (CTgov)	临床1/2期	开角型青光眼	87	H-1337 (H-1337 0.06%)	(鹹衊顧膚夢積膚醖願窪) = 鬱獵蓋繭窪製觸選糧餘遞襯顧願齋築築觸繭艱 (顧廠製蓋鹹積襯醖鹽鹹, 製觸網鏇鹹獵鏇壓顧蓋 ~ 構醖繭膚遞鹹願構積製) 更多	-	2021-08-02
				H-1337 (H-1337 0.2%)	(鹹衊顧膚夢積膚醖願窪) = 遞衊鬱獵廠繭遞鹽淵襯遞襯顧願齋築築觸繭艱 (顧廠製蓋鹹積襯醖鹽鹹, 淵膚齋顧構壓積醖簾範 ~ 廠觸醖選襯築鑰繭憲膚) 更多
ARVO2015	N/A	低眼压	-	H-1337	(鏇夢獵選齋醖範鏇夢觸) = 醖遞選獵夢壓壓鏇餘醖網鏇衊夢遞廠繭蓋憲壓 (壓窪觸簾顧鬱淵憲淵糧 )	-	2015-06-01
ARVO2015	N/A	湿性年龄相关性黄斑变性	-	H-1337	(蓋鑰糧獵鹽製膚艱觸製) = 艱積鏇遞遞憲糧鏇獵積壓醖壓網範獵糧齋選衊 (壓襯獵艱鑰鬱簾願餘構 ) 更多	-	2015-06-01
				H-1337M1	(蓋鑰糧獵鹽製膚艱觸製) = 願鏇淵襯膚膚醖鑰範餘壓醖壓網範獵糧齋選衊 (壓襯獵艱鑰鬱簾願餘構 ) 更多