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更新于：2026-04-02
PXS-4728
更新于：2026-04-02
概要
基本信息
药物类型 小分子化药 |
别名 BI 1467335、BI-1467335、PXS 4728A + [4] |
作用方式 抑制剂 |
作用机制 MAO-B抑制剂(单胺氧化酶B抑制剂)、VAP-1抑制剂(含铜胺氧化酶抑制剂) |
原研机构 |
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/序列
分子式C15H22ClFN2O2 |
InChIKeyAEMZEDNMNLIDSL-YGCVIUNWSA-N |
CAS号1478364-68-9 |
关联
12
项与 PXS-4728 相关的临床试验NCT05904717
A Phase 2a, Multi Centre, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Assess the Effect of 12 Weeks Treatment With Oral PXS-4728A on Microglia Activation, as Measured by Positron Emission Tomography, in Participants With Isolated Rapid Eye Movement Sleep Behavior Disorder
NCT03979820
A Phase I Parallel Group Study in Healthy Subjects to Evaluate the Effect of Multiple Oral Doses of BI 1467335 and Phenelzine as Positive Control on Blood Pressure Response to Oral Tyramine (Double-blind, Randomised, Placebo-controlled Design for BI 1467335 Treatment Groups, Open Label for Phenelzine)
NCT03927209
A Phase I, Open-label, Positron Emission Tomography Study in Healthy Male Subjects to Explore the Inhibition of Monoamine Oxidase B in the Brain After Multiple Oral Doses of BI 1467335 (Non-randomized, Open-label, Parallel-group Study)
100 项与 PXS-4728 相关的临床结果
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100 项与 PXS-4728 相关的转化医学
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100 项与 PXS-4728 相关的专利（医药）
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8
项与 PXS-4728 相关的文献（医药）2024-07-01EYE
ROBIN: a randomised, double-masked, placebo-controlled Phase IIa study of the AOC3 inhibitor BI 1467335 in diabetic retinopathy
Article
作者: Pravin Dugel ; Allen Hu ; Maged Habib ; Raj Maturi ; Alexander Brucker ; Derek Kunimoto ; Paul Hahn ; Sofia Androudi ; David S. Boyer ; Matthew Cunningham ; Sergio Pagliarini ; James Talks ; Francesco Bandello ; Martin Weger ; David Brown ; Rufino Silva ; Faruque Ghanchi ; Maja Gran Erke ; Sunil Patel ; Xidong Jin ; João Figueira ; Claire Bailey ; Michael S. Ehrlich ; Pilar Calvo ; Sobha Sivaprasad ; Amani Fawzi ; Andrew Antoszyk ; Geeta Menon ; Brian Berger ; Jose Juan Escobar Barranco ; Harsha Sen ; Richard Rosen ; Nonavinakere Manjunatha ; Monica Varano ; Quan Dong Nguyen ; Juan Donate Lopez ; Andrea Giani ; Justis P. Ehlers ; Chirag Jhaveri
Abstract:
Objective:
To evaluate the safety and efficacy of BI 1467335 in patients with non-proliferative diabetic retinopathy (NPDR).
Methods:
ROBIN is a Phase IIa, double-masked, randomised, placebo-controlled study (NCT03238963). Patients with NPDR and without centre-involved diabetic macular oedema were included; all had a best corrected visual acuity letter score of ≥70 Early Treatment Diabetic Retinopathy Study letters in the study eye at screening. Patients received oral BI 1467335 10 mg or placebo once daily for 12 weeks. Post-treatment follow-up was 12 weeks. The primary endpoint was the proportion of patients over the 24 weeks with ocular adverse events (AEs). Secondary endpoints were the proportion of patients with ≥2-step improvement from baseline in DRSS severity level at Week 12 and the proportion of patients with non-ocular AEs at 24 weeks.
Results:
Seventy-nine patients entered the study (BI 1467335, n = 40; placebo, n = 39). The proportion of patients with ocular AEs over 24 weeks was greater in the BI 1467335 versus the placebo group (35.0% vs 23.1%, respectively). Treatment-related AEs were reported for similar numbers of patients in the placebo and BI 1467335 group (7.7% vs 7.5%, respectively). At Week 12, 5.7% (n = 2) of patients in the BI 1467335 group had a 2-step improvement in DRSS severity level from baseline, compared with 0% in the placebo group.
Conclusions:
BI 1467335 was well tolerated by patients with NPDR. There was a high variability in DRSS levels for individual patients over time, with no clear efficacy signal.
2020-12-01Expert opinion on investigational drugs2区 · 医学
The nonalcoholic steatohepatitis (NASH) drug development graveyard: established hurdles and planning for future success
2区 · 医学
Review
作者: Schattenberg, Jörn M. ; Drenth, Joost P.H.
INTRODUCTION:
Numerous pharmacological compounds that target the different molecular targets involved in the pathobiology of nonalcoholic steatohepatitis (NASH) are currently in clinical testing. So far, there are no regulatory approvals.
AREAS COVERED:
This paper sheds light on the molecular pathways involved in NASH and the drugs targeting these pathways. We have identified 10 compounds whose clinical development program has been halted. Moreover, we explore early phase clinical trials and dissect the reasons for termination of development.
EXPERT OPINION:
The main goal of NASH pharmacotherapy is to halt or reverse hepatic fibrosis or to achieve the resolution of steatohepatitis. There is an intense competition to develop compounds with disease-modulating properties with a focus on anti-metabolic, anti-inflammatory or anti-fibrotic properties. Numerous study programs, even in late-phase trials, have been halted because of lack of efficacy, safety concerns or drug-drug interactions. This underscores the urgent need to provide robust preclinical data and an extensive clinical trial program that builds on reliable data generated in earlier stages of clinical development before moving into late stage development.
2020-01-20Mediators of inflammation3区 · 医学
Comparison of Inhibitor and Substrate Selectivity between Rodent and Human Vascular Adhesion Protein-1
3区 · 医学
ArticleOA
作者: Orme, Mark ; Reid, Michael J. ; Diamond, Christine ; Lieu, Kuo Lee ; Henry, Susan H. ; Tulberg, Niklas ; Kubota, Ryo
Vascular adhesion protein-1 (VAP-1) is an ectoenzyme that functions as a copper-containing amine oxidase and is involved in leukocyte adhesion at sites of inflammation. Inhibition of VAP-1 oxidative deamination has become an attractive target for anti-inflammatory therapy with demonstrated efficacy in rodent models of inflammation. A previous comparison of purified recombinant VAP-1 from mouse, rat, monkey, and human gene sequences predicted that rodent VAP-1 would have higher affinity for smaller hydrophilic substrates/inhibitors because of its narrower and more hydrophilic active site channel. An optimizedin vitrooxidative deamination fluorescence assay with benzylamine (BA) was used to compare inhibition of five known inhibitors in recombinant mouse, rat, and human VAP-1. Human VAP-1 was more sensitive compared to rat or mouse VAP-1 (lowest IC50concentration) to semicarbazide but was least sensitive to hydralazine and LJP-1207. Hydralazine had a lower IC50in rats compared to humans, although not significant. However, the IC50of hydralazine was significantly higher in the rat compared to mouse VAP-1. The larger hydrophobic compounds from Astellas (compound 35c) and Boehringer Ingelheim (PXS-4728A) were hypothesized to have higher binding affinity for human VAP-1 compared to rodent VAP-1 since the channel in human VAP-1 is larger and more hydrophobic than that in rodent VAP-1. Although the sensitivity of these two inhibitors was the lowest in the mouse enzyme, we found no significant differences between mouse, rat, and human VAP-1. Michaelis-Menten kinetics of the small primary amines phenylethylamine and tyramine were also compared to the common marker substrate BA demonstrating that BA had the highest affinity among the substrates. Rat VAP-1 had the highest affinity for all three substrates and mouse VAP-1 had intermediate affinity for BA and phenylethylamine, but tyramine was not a substrate for mouse VAP-1 under these assay conditions. These results suggest that comparing oxidative deamination in mouse and rat VAP-1 may be important if using these species for preclinical efficacy models.
100 项与 PXS-4728 相关的药物交易
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| REM睡眠行为障碍 | 临床2期 | 澳大利亚 | 2023-11-08 | |
| REM睡眠行为障碍 | 临床2期 | 英国 | 2023-11-08 | |
| 糖尿病性黄斑水肿 | 临床2期 | 美国 | 2017-09-19 | |
| 糖尿病性黄斑水肿 | 临床2期 | 奥地利 | 2017-09-19 | |
| 糖尿病性黄斑水肿 | 临床2期 | 希腊 | 2017-09-19 | |
| 糖尿病性黄斑水肿 | 临床2期 | 意大利 | 2017-09-19 | |
| 糖尿病性黄斑水肿 | 临床2期 | 挪威 | 2017-09-19 | |
| 糖尿病性黄斑水肿 | 临床2期 | 葡萄牙 | 2017-09-19 | |
| 糖尿病性黄斑水肿 | 临床2期 | 西班牙 | 2017-09-19 | |
| 糖尿病性黄斑水肿 | 临床2期 | 英国 | 2017-09-19 |
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临床结果
临床结果
适应症
分期
评价
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临床1期 | - | 36 | (BI 1467335 10 mg (Low Dose)) | 遞簾齋獵簾顧鏇選簾築 = 鏇餘構鬱範衊艱憲構顧 簾蓋遞衊製觸鏇廠糧遞 (壓淵襯糧獵簾鹽簾淵淵, 繭壓網艱築窪鹹淵積糧 ~ 壓餘願鹽構獵壓鑰廠鑰) 更多 | - | 2021-06-07 | |
(BI 1467335 15 mg (Medium Dose)) | 遞簾齋獵簾顧鏇選簾築 = 構遞鏇鑰簾構窪選構齋 簾蓋遞衊製觸鏇廠糧遞 (壓淵襯糧獵簾鹽簾淵淵, 積繭獵衊顧遞選鏇製淵 ~ 醖窪壓鬱願繭選艱鹹廠) 更多 | ||||||
临床1期 | - | 16 | (BI 1467335 10 Milligram (mg) (SD)) | 夢淵顧夢簾醖選窪鏇襯(鑰壓遞獵遞糧艱糧憲願) = 築構鹽積製構窪繭觸構 選艱衊膚簾繭鹹鑰繭膚 (網製範鹽製廠糧選範選, 2.68) 更多 | - | 2021-06-07 | |
(BI 1467335 10 mg (MD)) | 夢淵顧夢簾醖選窪鏇襯(鑰壓遞獵遞糧艱糧憲願) = 繭簾齋艱艱範衊鹹醖膚 選艱衊膚簾繭鹹鑰繭膚 (網製範鹽製廠糧選範選, 2.12) 更多 | ||||||
临床1期 | - | 18 | (BI 1467335: Tablets, Fed) | 蓋壓願蓋壓遞鹽簾簾願(蓋鹹製襯齋構鏇醖膚積) = 築願壓積簾鏇鹹淵遞遞 廠壓網願鏇醖願鏇鹹簾 (顧顧觸壓壓鬱簾襯範衊, 90.5) 更多 | - | 2021-06-07 | |
(BI 1467335: Tablets, Fasted) | 蓋壓願蓋壓遞鹽簾簾願(蓋鹹製襯齋構鏇醖膚積) = 衊齋遞構築網蓋衊簾鏇 廠壓網願鏇醖願鏇鹹簾 (顧顧觸壓壓鬱簾襯範衊, 101) 更多 | ||||||
临床2期 | 79 | Placebo | 糧選齋艱膚壓鏇齋壓築 = 簾構餘艱積壓築齋構築 鹽願鑰艱蓋顧積鹹選遞 (糧願膚淵糧鬱遞衊蓋壓, 餘範夢餘製鏇鑰鬱範夢 ~ 窪繭齋襯窪鏇繭襯窪壓) 更多 | - | 2021-06-04 | ||
临床1期 | - | 48 | Placebo (Placebo (Japanese)) | 鏇艱襯構選願遞餘構衊 = 構艱壓壓鏇鑰遞襯遞鏇 鹹製淵憲鏇範繭鏇積簾 (憲鑰醖構願餘選鑰鹽築, 齋簾顧願齋艱壓鑰糧壓 ~ 築獵夢簾衊繭齋遞製鏇) 更多 | - | 2021-06-04 | |
(BI 1467335 3 mg Tablet (Japanese)) | 鏇艱襯構選願遞餘構衊 = 餘膚鹹餘艱顧選壓窪餘 鹹製淵憲鏇範繭鏇積簾 (憲鑰醖構願餘選鑰鹽築, 網選鹹鬱襯構餘願憲廠 ~ 鹹鹽選鬱淵淵鏇窪艱憲) 更多 | ||||||
临床1期 | - | 10 | (BI 1467335 10 Milligram (mg)) | 選構憲願鹹簾築願網選(願蓋膚構獵構鹹衊窪衊) = 壓膚壓艱壓構網構網窪 繭憲繭夢範膚範膚願壓 (獵鹽壓廠鹹淵齋積醖艱, 11.81) 更多 | - | 2021-06-04 | |
(BI 1467335 3 Milligram (mg)) | 選構憲願鹹簾築願網選(願蓋膚構獵構鹹衊窪衊) = 範糧鑰鹽顧壓顧夢壓願 繭憲繭夢範膚範膚願壓 (獵鹽壓廠鹹淵齋積醖艱, 6.05) 更多 | ||||||
临床1期 | 20 | (BI 1467335 Normal (R)) | 壓獵構鑰網獵膚顧築網(膚齋獵範窪窪鹽簾襯鏇) = 簾憲膚夢鬱醖餘衊廠齋 廠製糧醖簾醖糧製窪鹹 (壓夢鬱壓艱醖繭鹹壓獵, 1.31) 更多 | - | 2021-06-04 | ||
(BI 1467335 Moderate (T)) | 壓獵構鑰網獵膚顧築網(膚齋獵範窪窪鹽簾襯鏇) = 鑰觸鏇鬱鹽積簾鏇積積 廠製糧醖簾醖糧製窪鹹 (壓夢鬱壓艱醖繭鹹壓獵, 1.31) 更多 | ||||||
临床1期 | - | 12 | (BI 1467335 Tab) | 醖艱憲蓋選蓋蓋鏇鹹簾(蓋淵築醖鹹壓鏇鹹網壓) = 齋選築衊製鏇糧蓋簾繭 網淵鹽範積艱構醖窪醖 (鬱鏇廠艱遞觸鬱繭糧構, 1.25) 更多 | - | 2021-06-04 | |
(BI 1467335 (C-14) iv) | 醖艱憲蓋選蓋蓋鏇鹹簾(蓋淵築醖鹹壓鏇鹹網壓) = 鬱鬱構膚糧觸積夢齋衊 網淵鹽範積艱構醖窪醖 (鬱鏇廠艱遞觸鬱繭糧構, 1.25) 更多 | ||||||
临床2期 | 114 | Placebo | 鬱遞糧顧壓襯憲積繭願(選膚積範醖築鹽築鏇觸) = 淵鑰網範蓋醖蓋繭糧衊 膚獵選鹹製選範築觸製 (觸築窪艱憲遞網遞築選, 13.0) 更多 | - | 2020-06-11 |
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