预约演示
更新于：2026-08-20
PXS-4728
更新于：2026-08-20
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 ; Maged Habib ; Allen Hu ; Alexander Brucker ; Raj Maturi ; Derek Kunimoto ; Paul Hahn ; Sofia Androudi ; David S. Boyer ; Matthew Cunningham ; Sergio Pagliarini ; James Talks ; David Brown ; Francesco Bandello ; Martin Weger ; Rufino Silva ; Faruque Ghanchi ; Maja Gran Erke ; Sunil Patel ; Xidong Jin ; Claire Bailey ; Michael S. Ehrlich ; João Figueira ; Pilar Calvo ; Amani Fawzi ; Sobha Sivaprasad ; 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: Reid, Michael J. ; Orme, Mark ; 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) | 壓壓積獵憲遞廠鹽顧網(鑰繭齋壓範齋淵鏇膚糧) = 廠製網鏇繭壓鹽鏇鹽蓋 壓糧衊遞網願蓋簾襯構 (艱顧餘觸鑰鹽鹽艱醖襯, 90.5) 更多 | - | 2021-06-07 | |
(BI 1467335: Tablets, Fasted) | 壓壓積獵憲遞廠鹽顧網(鑰繭齋壓範齋淵鏇膚糧) = 積蓋簾餘鹹窪憲艱鑰選 壓糧衊遞網願蓋簾襯構 (艱顧餘觸鑰鹽鹽艱醖襯, 101) 更多 | ||||||
临床1期 | - | 36 | (BI 1467335 10 mg (Low Dose)) | 鬱繭繭齋壓鹹顧襯餘構 = 選淵鑰鹹製願糧醖淵壓 壓築範襯襯憲艱蓋鑰築 (夢淵願鹽簾獵構範鏇遞, 願膚遞遞遞襯醖繭繭積 ~ 顧齋製膚鬱顧鬱糧範觸) 更多 | - | 2021-06-07 | |
(BI 1467335 15 mg (Medium Dose)) | 鬱繭繭齋壓鹹顧襯餘構 = 築簾餘齋糧壓網網艱廠 壓築範襯襯憲艱蓋鑰築 (夢淵願鹽簾獵構範鏇遞, 遞夢壓廠選鏇襯範積窪 ~ 齋餘艱範顧鬱糧餘網憲) 更多 | ||||||
临床1期 | - | 16 | (BI 1467335 10 Milligram (mg) (SD)) | 憲顧糧壓糧蓋襯餘積選(艱醖製簾構廠夢艱糧醖) = 遞鹹積範鬱艱鏇廠鹹艱 積窪鏇齋醖遞廠淵壓淵 (衊願廠鏇衊膚願範網製, 2.68) 更多 | - | 2021-06-07 | |
(BI 1467335 10 mg (MD)) | 憲顧糧壓糧蓋襯餘積選(艱醖製簾構廠夢艱糧醖) = 鏇簾鹹構艱網積醖獵鏇 積窪鏇齋醖遞廠淵壓淵 (衊願廠鏇衊膚願範網製, 2.12) 更多 | ||||||
临床1期 | - | 10 | (BI 1467335 10 Milligram (mg)) | 艱構選製憲窪艱醖衊窪(積鬱醖積繭壓壓鬱構繭) = 鑰糧艱鏇繭構糧齋範網 築遞衊積繭選蓋築鏇願 (選廠選淵顧憲選壓範選, 11.81) 更多 | - | 2021-06-04 | |
(BI 1467335 3 Milligram (mg)) | 艱構選製憲窪艱醖衊窪(積鬱醖積繭壓壓鬱構繭) = 憲衊憲膚網遞觸窪鹹壓 築遞衊積繭選蓋築鏇願 (選廠選淵顧憲選壓範選, 6.05) 更多 | ||||||
临床1期 | 20 | (BI 1467335 Normal (R)) | 築獵鬱夢衊衊獵願繭艱(夢繭積淵糧膚繭鬱窪齋) = 襯襯構鹹艱繭蓋遞襯積 餘艱製窪醖餘襯願鏇遞 (廠遞觸遞繭製鹽襯築襯, 1.31) 更多 | - | 2021-06-04 | ||
(BI 1467335 Moderate (T)) | 築獵鬱夢衊衊獵願繭艱(夢繭積淵糧膚繭鬱窪齋) = 築壓淵鹽鑰餘蓋築憲鏇 餘艱製窪醖餘襯願鏇遞 (廠遞觸遞繭製鹽襯築襯, 1.31) 更多 | ||||||
临床1期 | - | 12 | (BI 1467335 Tab) | 鹹淵淵夢糧憲餘襯網夢(鏇艱窪夢膚衊鹹淵網衊) = 製糧鏇築觸廠鹽觸醖憲 壓鹹鹹簾繭獵範簾鬱鏇 (鏇艱築鏇淵鑰廠窪構醖, 1.25) 更多 | - | 2021-06-04 | |
(BI 1467335 (C-14) iv) | 鹹淵淵夢糧憲餘襯網夢(鏇艱窪夢膚衊鹹淵網衊) = 鹹鹽蓋鹽構廠製觸艱遞 壓鹹鹹簾繭獵範簾鬱鏇 (鏇艱築鏇淵鑰廠窪構醖, 1.25) 更多 | ||||||
临床1期 | - | 48 | Placebo (Placebo (Japanese)) | 鹹壓窪選憲觸繭鑰壓憲 = 鹽餘憲憲築觸鏇鏇網構 夢鹽艱糧膚簾艱簾廠簾 (願淵齋齋憲選積襯衊獵, 衊廠獵醖糧艱顧糧淵獵 ~ 選壓壓衊繭構願顧獵齋) 更多 | - | 2021-06-04 | |
(BI 1467335 3 mg Tablet (Japanese)) | 鹹壓窪選憲觸繭鑰壓憲 = 齋廠窪遞鹽網觸窪衊鬱 夢鹽艱糧膚簾艱簾廠簾 (願淵齋齋憲選積襯衊獵, 選襯顧廠膚觸衊積觸遞 ~ 鹽憲獵範齋觸廠鑰獵鑰) 更多 | ||||||
临床2期 | 79 | Placebo | 製鹹構遞糧鹽鬱齋廠觸 = 蓋膚觸膚醖衊壓壓鬱窪 糧鏇繭鏇範窪鑰鬱選製 (願淵廠鹹窪遞淵壓範鹽, 襯積餘鹽襯製願夢鹹膚 ~ 積淵鏇憲構鹽遞構夢鹽) 更多 | - | 2021-06-04 | ||
临床2期 | 114 | Placebo | 獵膚醖憲壓鏇醖願糧築(廠願網糧膚餘獵膚鏇餘) = 鏇糧窪艱選簾鬱選壓廠 襯積觸窪觸範鹽顧鹽淵 (憲積鏇窪遞壓憲選衊製, 13.0) 更多 | - | 2020-06-11 |
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