HL-217(HL-217) - 药物靶点：PDGFRβ x VEGF_在研适应症：黄斑变性_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PDGFRβ x VEGF

作用机制

PDGFRβ抑制剂(血小板衍生生长因子受体β抑制剂)、VEGF抑制剂(血管内皮生长因子抑制剂)

治疗领域

遗传病与畸形眼部疾病

在研适应症

黄斑变性

非在研适应症-

原研机构

Hanlim Pharm Co., Ltd.

在研机构

Hanlim Pharm Co., Ltd.

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)-

特殊审评-

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结构

分子式C23H27ClN4O4

InChIKeyXPQNJJQQAZIHMI-QZNHQXDQSA-N

CAS号571141-49-6

关联

4

项与 HL-217 相关的临床试验

EUCTR2019-000642-35-BG / Unknown status临床2期

A phase IIa randomized, double-blind, multicentre study to evaluate safety and efficacy of HL217 topical ophthalmologic solution in the treatment of exudative Age-Related Macular Degeneration (AMD)

开始日期2019-11-11

申办/合作机构

Hanlim Pharm Co., Ltd.

EUCTR2019-000642-35-FR / Not yet recruiting临床2期

A phase IIa randomized, double-blind, multicentre study to evaluate safety and efficacy of HL217 topical ophthalmologic solution in the treatment of exudative Age-Related Macular Degeneration (AMD)

开始日期2019-09-19

申办/合作机构

Hanlim Pharm Co., Ltd.

NCT03648346 / Completed临床1期

A Dose Block-randomized, Double Blind, Placebo Controlled, Dose-escalation Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetics After Multiple Dosing of HL217 Eye Drop in Healthy Male Subjects

The study is a single center, double-blind, randomized, parallel group, multiple ascending dose study in 16 healthy male volunteers. Subjects will receive multiple eye drop doses during 14 days of the treatment (HL217 or placebo according to the randomization). There will be 2 cohorts of 8 subjects (6 HL217 vs 2 placebo) receiving the following doses:
Cohort 1 : two drops of 3 mg/mL of the treatment in one eye twice a day (low dose),
Cohort 2 : two drops of 3 mg/mL of the treatment in one eye 4 times a day (high dose).

开始日期2018-04-04

申办/合作机构

Hanlim Pharm Co., Ltd.

100 项与 HL-217 相关的临床结果

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100 项与 HL-217 相关的转化医学

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100 项与 HL-217 相关的专利（医药）

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9

项与 HL-217 相关的文献（医药）

2022-02-01·Biomedicine & Pharmacotherapy2区 · 医学

KR-31831 improves survival and protects hematopoietic cells and radiosensitive tissues against radiation-induced injuries in mice

2区 · 医学

Article

作者: Lee, Ju Hee ; Oh, Kwang-Seok ; Seo, Ho Won ; Lee, Jeong Hyun ; Lee, Byung Ho ; Yi, Hyuna

This study explored the radioprotective effects and possible underlying mechanisms of KR-31831 against radiation-induced injury in a mouse model. KR-31831 (30 and 50 mg/kg) was administered to mice 24 h and 30 min before exposure to a single lethal or sublethal dose of whole-body irradiation (WBI) (7 or 4 Gy, respectively). These animals were then evaluated for changes in mortality, various hematological and biochemical parameters, and histological features in response to these treatments. In addition, RNA sequencing was used to profile the radiation-induced transcriptomic response in the bone marrow cells. The results showed that KR-31831 dose-dependently prolonged the 30-day survival period and prevented damage to radiation-sensitive organs, such as the intestine and testis, in response to WBI. Damage to the hematopoietic system was also notably improved in the KR-31831-treated mice, as evidenced by an increase in bone marrow and peripheral blood cells, as well as recovery of the histopathological characteristics of the bone marrow. These protective effects were achieved, at least in part, via the suppression of radiation-induced increases in apoptotic cell death and erythropoietin levels in the plasma. Furthermore, the gene expression profiles of the bone marrow cells of the WBI-treated mice suggested that KR-31831 upregulates the expression of the genes involved in regulating apoptosis and modulating the immune response, both of which are required for protecting the bone marrow. These results suggest the potential therapeutic efficacy of KR-31831 for protection against radiation-induced injury.

2015-01-01·Biochemical and Biophysical Research Communications3区 · 生物学

HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr−/− mice

3区 · 生物学

Article

作者: Kim, Hyun-Gyu ; Cho, Yun-Seok ; Kim, Jin Sook ; Kim, Junghyun ; Lee, Yun Mi ; Jo, Kyuhyung ; Kim, Chan-Sik ; Lee, Geun-Hyeog ; Sohn, Eunjin

HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr(-/-)) mice. In three-week-old male Vldlr(-/-) mice, HL-217 (1.5 or 3mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr(-/-) mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRβ interaction (IC50=38.9 ± 0.7 μM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB.

2012-11-19·Investigative Opthalmology & Visual Science2区 · 医学

Dynamic Contrast-Enhanced MRI for Assessing Therapeutic Response of Choroidal Neovascularization in a Rat Model

2区 · 医学

ArticleOA

作者: Jae-Hun Kim ; Jung Hee Lee ; Ji Hoon Cha ; Don-il Ham ; Sun I. Kim ; Julius Juhyun Chung ; Jaemoon Yoon ; Geun Ho Im ; Jehoon Yang

PURPOSEWe evaluated the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a noninvasive biomarker of choroidal neovascularization (CNV) and its utility as a tool for monitoring therapeutic response in laser-induced rat CNV models.METHODSCNV was induced in the right eyes of 14 rats using a laser. Rats (n = 7) were treated daily for 14 days with a candidate drug (KR-31831, 50 mg/kg of body weight) having antiangiogenic effects, whereas control rats (n = 7) were treated with the vehicle alone (10% cremophor, 10% absolute ethyl alcohol, and 80% saline). DCE-MRI examinations were performed on the day before surgery (D - 1), and 3, 7, and 14 days after surgery (D + 3, D + 7, and D + 14), from which pharmacokinetic parameters (K(trans), v(e), v(p)) were calculated. Angiography was performed to visualize CNV using FITC-labeled high molecular weight dextran after MRI on D + 14. The paired Wilcoxon test and Mann-Whitney U test were performed for statistical analysis.RESULTSThe K(trans) and v(e) values of the CNV-induced right eyes were significantly higher than those of the intact eyes in control rats at D + 14 (P < 0.05). In the CNV-induced eyes, the relative K(trans) and v(e) values of the KR-31831-treated group were significantly lower than those of the nontreated group at D + 14 (P < 0.05). The angiography showed that decreased CNV was observed in rats treated with KR-31831.CONCLUSIONSQuantitative DCE-MRI produces noninvasive biomarker of CNV, thus allowing monitoring of therapeutic response of antiangiogenic drugs in neovascular age-related macular degeneration (AMD).

100 项与 HL-217 相关的药物交易

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