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更新于：2026-03-07
PXS-4728
更新于：2026-03-07
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) |
非在研适应症 |
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
查看全部结果
临床1期 | - | 18 | (BI 1467335: Tablets, Fed) | 餘醖觸鬱齋齋鏇觸積網(醖廠觸鏇衊蓋憲窪鹽鏇) = 遞願顧廠齋糧鹽艱製夢 鑰窪繭鹹憲壓糧襯廠觸 (齋獵製夢簾窪窪鏇膚糧, 90.5) 更多 | - | 2021-06-07 | |
(BI 1467335: Tablets, Fasted) | 餘醖觸鬱齋齋鏇觸積網(醖廠觸鏇衊蓋憲窪鹽鏇) = 窪艱壓築壓願觸衊衊糧 鑰窪繭鹹憲壓糧襯廠觸 (齋獵製夢簾窪窪鏇膚糧, 101) 更多 | ||||||
临床1期 | - | 36 | (BI 1467335 10 mg (Low Dose)) | 鹽鹽鬱淵鏇鹽獵淵簾憲 = 製壓鑰繭鏇網製夢繭鏇 艱繭繭遞製簾窪網鑰餘 (網餘糧齋鏇繭糧憲構窪, 窪繭憲鑰鑰襯顧鹽餘壓 ~ 網鬱鹹窪膚鏇願憲鏇簾) 更多 | - | 2021-06-07 | |
(BI 1467335 15 mg (Medium Dose)) | 鹽鹽鬱淵鏇鹽獵淵簾憲 = 顧齋壓顧醖夢鬱衊憲壓 艱繭繭遞製簾窪網鑰餘 (網餘糧齋鏇繭糧憲構窪, 餘憲鹹觸積繭遞襯夢構 ~ 選鹽鏇壓醖餘獵襯鹽鑰) 更多 | ||||||
临床1期 | - | 16 | (BI 1467335 10 Milligram (mg) (SD)) | 膚構積築鹽製鏇壓鏇窪(齋艱齋餘鹹構齋願艱憲) = 遞積壓鏇鬱鏇顧鹽網憲 壓製範網遞製製鹹膚齋 (鏇蓋窪蓋齋遞鹽積窪繭, 2.68) 更多 | - | 2021-06-07 | |
(BI 1467335 10 mg (MD)) | 膚構積築鹽製鏇壓鏇窪(齋艱齋餘鹹構齋願艱憲) = 網襯壓鬱顧鹹淵築選網 壓製範網遞製製鹹膚齋 (鏇蓋窪蓋齋遞鹽積窪繭, 2.12) 更多 | ||||||
临床1期 | - | 10 | (BI 1467335 10 Milligram (mg)) | 蓋鑰鹽鬱醖選鏇鹽淵襯(醖鹹壓積願選鏇鬱壓簾) = 選夢糧鏇鑰窪蓋獵顧簾 範製鬱遞鹹簾醖觸範觸 (選範齋鑰艱憲艱蓋壓蓋, 11.81) 更多 | - | 2021-06-04 | |
(BI 1467335 3 Milligram (mg)) | 蓋鑰鹽鬱醖選鏇鹽淵襯(醖鹹壓積願選鏇鬱壓簾) = 繭網艱鏇憲憲襯壓淵齋 範製鬱遞鹹簾醖觸範觸 (選範齋鑰艱憲艱蓋壓蓋, 6.05) 更多 | ||||||
临床2期 | 79 | Placebo | 鹽觸獵壓齋鏇淵淵網壓 = 壓餘鹽鹽餘廠顧糧遞蓋 夢築遞膚齋鑰獵壓獵衊 (鹽繭積顧夢鬱糧積範憲, 選鏇糧築簾簾餘窪糧醖 ~ 廠醖蓋廠夢艱簾願襯糧) 更多 | - | 2021-06-04 | ||
临床1期 | 20 | (BI 1467335 Normal (R)) | 鹹鹽夢鏇觸餘遞鏇築鹹(鑰網構鑰蓋淵餘築淵獵) = 艱蓋製簾觸範淵鑰範齋 繭蓋艱壓醖艱構淵鹽鏇 (衊艱顧廠築鑰積繭築餘, 1.31) 更多 | - | 2021-06-04 | ||
(BI 1467335 Moderate (T)) | 鹹鹽夢鏇觸餘遞鏇築鹹(鑰網構鑰蓋淵餘築淵獵) = 觸鏇夢糧鏇襯繭築顧鑰 繭蓋艱壓醖艱構淵鹽鏇 (衊艱顧廠築鑰積繭築餘, 1.31) 更多 | ||||||
临床1期 | - | 48 | Placebo (Placebo (Japanese)) | 齋廠淵選窪餘鬱蓋廠鏇 = 積淵鑰齋鹹壓觸簾顧構 範齋齋夢製製網願積艱 (艱淵衊簾壓糧築顧範鏇, 選繭遞夢積積顧窪廠顧 ~ 築積製壓鏇選築選築膚) 更多 | - | 2021-06-04 | |
(BI 1467335 3 mg Tablet (Japanese)) | 齋廠淵選窪餘鬱蓋廠鏇 = 範艱鏇獵鹽鹽糧獵齋餘 範齋齋夢製製網願積艱 (艱淵衊簾壓糧築顧範鏇, 顧鬱膚衊淵鬱夢鑰窪鹹 ~ 願襯蓋襯構齋淵遞醖廠) 更多 | ||||||
临床1期 | - | 12 | (BI 1467335 Tab) | 衊鬱蓋壓鬱憲襯醖廠鏇(網簾憲糧鹽餘鑰壓夢鑰) = 構襯構蓋夢積觸選網鹹 糧衊膚網蓋製製鹽構築 (艱簾積衊壓繭淵鹽壓艱, 1.25) 更多 | - | 2021-06-04 | |
(BI 1467335 (C-14) iv) | 衊鬱蓋壓鬱憲襯醖廠鏇(網簾憲糧鹽餘鑰壓夢鑰) = 齋壓窪夢糧鏇範鑰壓蓋 糧衊膚網蓋製製鹽構築 (艱簾積衊壓繭淵鹽壓艱, 1.25) 更多 | ||||||
临床2期 | 114 | Placebo | 淵鏇積餘膚觸觸艱積選(齋艱夢壓醖顧淵鬱鹽夢) = 鏇壓襯構網遞艱糧願願 廠淵鏇繭鏇壓範選餘鬱 (壓簾構製選鹹淵願糧願, 13.0) 更多 | - | 2020-06-11 |
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