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更新于：2026-06-03
PXS-4728
更新于：2026-06-03
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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11
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
查看全部结果
临床1期 | - | 16 | (BI 1467335 10 Milligram (mg) (SD)) | 願遞鹽網衊醖壓襯醖構(壓糧蓋製壓簾顧繭糧製) = 餘遞積鹽選憲鬱蓋願醖 範築鹽鹽憲餘觸築鏇獵 (鬱夢鹹夢襯廠築築蓋鏇, 2.68) 更多 | - | 2021-06-07 | |
(BI 1467335 10 mg (MD)) | 願遞鹽網衊醖壓襯醖構(壓糧蓋製壓簾顧繭糧製) = 網廠獵鏇繭鹹網衊壓網 範築鹽鹽憲餘觸築鏇獵 (鬱夢鹹夢襯廠築築蓋鏇, 2.12) 更多 | ||||||
临床1期 | - | 36 | (BI 1467335 10 mg (Low Dose)) | 積選艱壓淵獵膚窪膚艱 = 廠廠壓鹹淵壓襯鹽膚範 積簾鬱齋繭鹽遞網簾鬱 (鏇餘餘範艱糧糧獵顧艱, 鑰範鹽壓鬱夢夢蓋鹹顧 ~ 膚繭遞顧顧壓遞鹹構鏇) 更多 | - | 2021-06-07 | |
(BI 1467335 15 mg (Medium Dose)) | 積選艱壓淵獵膚窪膚艱 = 網鹽鹽窪製艱構願廠憲 積簾鬱齋繭鹽遞網簾鬱 (鏇餘餘範艱糧糧獵顧艱, 範繭蓋觸獵窪糧鏇糧鹽 ~ 鑰網夢簾築願鹹襯鑰鏇) 更多 | ||||||
临床1期 | - | 18 | (BI 1467335: Tablets, Fed) | 衊鑰齋廠蓋範窪簾網淵(膚鏇夢膚夢鹹構夢簾鹹) = 艱廠遞廠醖簾獵艱鏇憲 餘憲網襯遞襯淵鹽憲網 (鹽餘鬱衊糧襯鬱選憲範, 90.5) 更多 | - | 2021-06-07 | |
(BI 1467335: Tablets, Fasted) | 衊鑰齋廠蓋範窪簾網淵(膚鏇夢膚夢鹹構夢簾鹹) = 製艱鑰艱夢衊壓壓襯獵 餘憲網襯遞襯淵鹽憲網 (鹽餘鬱衊糧襯鬱選憲範, 101) 更多 | ||||||
临床1期 | - | 10 | (BI 1467335 10 Milligram (mg)) | 鹽膚壓醖壓觸鑰遞衊衊(蓋積築簾顧顧構糧齋淵) = 鏇窪鬱願醖願艱觸壓製 顧鬱鑰蓋鑰襯觸艱齋鬱 (範願壓構餘鹹窪築餘蓋, 11.81) 更多 | - | 2021-06-04 | |
(BI 1467335 3 Milligram (mg)) | 鹽膚壓醖壓觸鑰遞衊衊(蓋積築簾顧顧構糧齋淵) = 製遞鹹鬱鹽壓網夢築範 顧鬱鑰蓋鑰襯觸艱齋鬱 (範願壓構餘鹹窪築餘蓋, 6.05) 更多 | ||||||
临床1期 | - | 48 | Placebo (Placebo (Japanese)) | 齋製簾製選製積艱鏇糧 = 艱淵鹹襯觸築憲糧艱製 構選鑰憲簾積繭築築淵 (窪襯築觸觸鬱憲鏇夢餘, 製製積蓋繭鑰製範鏇範 ~ 齋夢獵構糧衊鏇蓋醖積) 更多 | - | 2021-06-04 | |
(BI 1467335 3 mg Tablet (Japanese)) | 齋製簾製選製積艱鏇糧 = 廠憲鹹鹽壓夢鏇願餘憲 構選鑰憲簾積繭築築淵 (窪襯築觸觸鬱憲鏇夢餘, 選淵壓觸觸觸遞鏇顧願 ~ 簾鹹鹽簾糧膚襯積膚糧) 更多 | ||||||
临床1期 | - | 12 | (BI 1467335 Tab) | 鏇遞衊壓憲廠製選獵窪(鬱繭顧夢艱網衊糧憲窪) = 衊鬱餘鏇觸繭範製鬱襯 鏇壓構廠製鏇夢襯蓋鬱 (窪壓壓築糧窪膚觸構鏇, 1.25) 更多 | - | 2021-06-04 | |
(BI 1467335 (C-14) iv) | 鏇遞衊壓憲廠製選獵窪(鬱繭顧夢艱網衊糧憲窪) = 膚鏇築蓋製鑰夢艱廠醖 鏇壓構廠製鏇夢襯蓋鬱 (窪壓壓築糧窪膚觸構鏇, 1.25) 更多 | ||||||
临床1期 | 20 | (BI 1467335 Normal (R)) | 製積繭積壓築獵築齋膚(廠製構獵構願夢願願壓) = 窪構衊醖襯淵觸鏇壓鏇 遞簾簾衊糧鑰窪淵鑰膚 (簾觸鏇鹹構齋製膚構構, 1.31) 更多 | - | 2021-06-04 | ||
(BI 1467335 Moderate (T)) | 製積繭積壓築獵築齋膚(廠製構獵構願夢願願壓) = 醖壓鹹夢齋糧鏇積糧窪 遞簾簾衊糧鑰窪淵鑰膚 (簾觸鏇鹹構齋製膚構構, 1.31) 更多 | ||||||
临床2期 | 79 | Placebo | 積遞選鹹範醖觸範衊鹹 = 餘鹹遞艱糧選顧顧艱壓 願齋遞蓋廠衊餘獵襯襯 (膚鹹蓋築窪壓獵齋築鹽, 壓壓範範築糧遞糧窪觸 ~ 醖廠廠淵齋淵襯夢製鏇) 更多 | - | 2021-06-04 | ||
临床2期 | 114 | Placebo | 鬱觸遞蓋選餘餘蓋鏇淵(獵獵選願淵選糧遞鬱膚) = 範鬱鑰蓋鹹壓鏇膚襯窪 淵鏇鏇網蓋製廠夢積網 (鑰鏇觸窪網鹹築遞餘構, 13.0) 更多 | - | 2020-06-11 |
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