An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of BAY 2395840 in Participants With Moderate Renal Impairment and in Healthy Male and Female Participants With Normal Renal Function

Researchers are looking for a better way to treat people who have inflammatory conditions.
Inflammatory conditions may result from an increased activation of the body's natural defenses (the immune system) and are characterized by swelling, redness, heat, and pain.
The study treatment BAY2395840 is under development for use in inflammatory conditions. It works by blocking a protein, the B1 receptor, whose activation is involved in inflammatory responses.
The main purpose of this study is to learn how a single dose of BAY2395840 moves into, through and out of the body in participants with a moderate reduction of kidney function compared to matched participants with normal kidney function.
To answer this, the researchers will compare:
the (average) total level of BAY2395840 in the blood (also known as AUC), and
the (average) highest level of BAY2395840 in the blood (also known as Cmax) between the two groups of participants. The participants do not benefit from this study. However, the study will provide information on how to use BAY2395840 in later studies in people with inflammatory conditions. As some people with these conditions may also have kidney problems, this study is done in participants with moderate reduction of kidney function to characterize the use of BAY2395840 in this patient group.
All participants will take a single dose of BAY2395840 as tablets. Each participant will be in the study for up to 5 weeks. They will stay in-house for 4 days, including one treatment day. In addition, one visit before and one visit after the in-house phase to the study site is planned.

开始日期2023-05-15

申办/合作机构

Bayer AG

NCT05563454 / Completed临床1期

A Randomized, Placebo-controlled, Single-blind, Dose Escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of BAY 2395840 After Single and Multiple Dose in Japanese Healthy Male Participants

Researchers are looking for a better way to treat people who have diabetic neuropathic pain (DNP).
DNP is pain due to damage to the nerves in the extremities that can occur in patients with diabetes as a result of blood sugar levels being too high for too long.
BAY2395840 works by blocking specific receptors. A receptor is a protein inside or on the surface of a cell that binds to a specific substance and causes a specific effect in the cell. BAY2395840 specifically blocks so-called bradykinin B1 receptor, whose activation is involved in inflammatory responses. This blockage may help to relieve pain and inflammation.
BAY2395840 has already been studied in clinical studies with European people. However, data for Japanese people are still missing. The participants of this study do not benefit from this study. However, the study will provide information on how to use BAY2395840 in later studies with Japanese people.
The main purpose of this study is to learn how safe the study drug BAY2395840 is and how it affects the body if given in single and in repetitive doses to Japanese healthy male participants.
To answer this question, the researchers will collect and analyze the medical problems the participants have after taking BAY2395840 and that may or may not be related to the study treatments. These medical problems are also known as "adverse events".
In addition, the study team will learn how BAY2395840 moves into, through and out of the body if given in single and in repetitive doses to Japanese healthy male participants. For this, the researchers will collect data on:
the (average) highest level of BAY2395840 in the blood (also referred to as Cmax)
the (average) total level of BAY2395840 in the blood (also referred to as AUC) during the treatment period with the study drug on day 1 and for the repetitive dose group only (see below), on day 7.
Subsequently, the study team will compare the data between those participants who received the study drug BAY2395840 (from different dosing groups) and those participants who received placebo. A placebo is a treatment that looks like a medicine but does not have any medicine in it.
All study participants will be randomly (by chance) assigned to 1 of 5 treatment groups. Dependent on the treatment group, the participants will either take:
a single dose of the lowest, middle and highest BAY2395840 dose (treatment groups 1 to 3)
repetitive doses of the highest BAY2395840 dose (treatment group 4) or
placebo (treatment group 5).
The participants will take their treatments as dosage form 1 after diet 1. The treatment period with repetitive doses of BAY2395840 will be 7 subsequent days.
The participants from treatment groups 1 to 3 will have an in house-period of 8 days including 7 overnight stays. The participants from treatment group 4 will have an in house-period of 12 days including 11 overnight stays. The study duration will be approximately 6 weeks per participant for dose groups 1 to 3 and approximately 7 weeks per participant for dose group 4.
During the study, the study team will:
take blood and urine samples
do physical examinations
check the vital signs such as blood pressure, heart rate, body temperature
examine heart health using electrocardiogram (ECG).
About 10 to 14 days after the participants take their last treatment, the study doctors and their team will check the participants' health.

开始日期2022-10-11

申办/合作机构

Bayer AG

EUCTR2021-001392-17-DE / Not yet recruiting临床2期

A randomized, double-blind, cross-over, placebo-controlled, multi-center, Phase 2a study to assess the safety and efficacy of BAY 2395840 in patients with diabetic neuropathic pain.

开始日期2022-03-08

申办/合作机构

Bayer AG

100 项与 B1 receptor 相关的临床结果

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100 项与 B1 receptor 相关的转化医学

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0 项与 B1 receptor 相关的专利（医药）

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1,092

项与 B1 receptor 相关的文献（医药）

2024-01-29·Computers in biology and medicine

Possible pharmacological targets and mechanisms of sivelestat in protecting acute lung injury.

Article

作者: Jiajia Ren ; Guorong Deng ; Ruohan Li ; Xuting Jin ; Jueheng Liu ; Jiamei Li ; Ya Gao ; Jingjing Zhang ; Xiaochuang Wang ; Gang Wang

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening syndrome induced by various diseases, including COVID-19. In the progression of ALI/ARDS, activated neutrophils play a central role by releasing various inflammatory mediators, including elastase. Sivelestat is a selective and competitive inhibitor of neutrophil elastase. Although its protective effects on attenuating ALI/ARDS have been confirmed in several models of lung injury, clinical trials have presented inconsistent results on its therapeutic efficacy. Therefore, in this report, we used a network pharmacology approach coupled with animal experimental validation to unravel the concrete therapeutic targets and biological mechanisms of sivelestat in treating ALI/ARDS. In bioinformatic analyses, we found 118 targets of sivelestat against ALI/ARDS, and identified six hub genes essential for sivelestat treatment of ALI/ARDS, namely ERBB2, GRB2, PTK2, PTPN11, ESR1, and CCND1. We also found that sivelestat targeted several genes expressed in human lung microvascular endothelial cells after lipopolysaccharide (LPS) treatment at 4 h (ICAM-1, PTGS2, RND1, BCL2A1, TNF, CA2, and ADORA2A), 8 h (ICAM-1, PTGS2, RND1, BCL2A1, MMP1, BDKRB1 and SLC40A1), and 24 h (ICAM-1). Further animal experiments showed that sivelestat was able to attenuate LPS-induced ALI by inhibiting the overexpression of ICAM-1, VCAM-1, and PTGS2 and increasing the phosphorylation of PTK2. Taken together, the bioinformatic findings and experimentative data indicate that the therapeutic effects of sivelestat against ALI/ARDS mainly focus on the early stage of ALI/ARDS by pharmacological modulation of inflammatory reaction, vascular endothelial injury, and cell apoptosis-related molecules.

2024-01-16·ACS omega

Apolipoprotein E3 Containing Nanodiscs as Vehicles for Transport and Targeted Delivery of Flavonoid Luteolin

Article

作者: Benedicto, Vernon Gil Laylo ; Haguar, Zahraa ; Abdulhasan, Abbas ; Narayanaswami, Vasanthy

Luteolin is a flavonoid that possesses multiple beneficial biological properties, such as anticancer, antioxidant, and anti-inflammatory effects. The objective of this study is to test the hypothesis that luteolin can be transported across a cell via a nanodisc delivery system and delivered to intracellular sites. Luteolin was incorporated into reconstituted high-density lipoprotein complexes made up of apolipoprotein E3 (apoE3) N-terminal domain (apoE3NT) and 1,2-dimystrioyl-sn-glycero-3-phosphocholine. ApoE3NT confers the ability on nanodiscs to traverse the plasma membrane via low-density lipoprotein receptor or scavenger receptor-B1. Physicochemical characterization revealed that the nanodiscs were 17-22 nm in diameter as demonstrated by native polyacrylamide gel electrophoresis and dynamic lightering analysis and ∼660 kDa in size, with a luteolin content of ∼4 luteolin molecules/nanodisc. Luteolin appeared to be embedded in the nonpolar core of nanodiscs, as revealed by fluorescence quenching and polarization analysis and spectroscopic characterization. The presence of luteolin did not affect the ability of apoE3NT to mediate binding and cellular uptake of luteolin containing nanodiscs in macrophages, as inferred from immunofluorescence analysis that revealed apoE- and lipid-related fluorescence as punctate perinuclear vesicles and from flow cytometry studies. Lastly, luteolin appeared to be localized in the nucleus, having escaped the lysosomes following disassembly of the nanodiscs as suggested by fluorescence spectroscopy and microscopy analyses. Taken together, nanodiscs offer the potential to effectively transport luteolin and potentially therapeutic drugs into perinuclear sites in cells, where they can be available to enter the nucleus.

2024-01-05·Cancers

Kinin Receptors and Kinin-Related Gene Expression in Astrocytic Brain Tumors.

Article

作者: Izabela Stadnicka ; Barbara Strzałka-Mrozik ; Magdalena Kimsa-Dudek ; Wojciech Kaspera ; Andrzej Plewka ; Wojciech Szopa ; Antoni Stadnicki

Kinins are a set of peptides present in tissues that are involved in the inflammatory response and cancer progression. However, studies showing the expression of kinin receptors in human glioma samples are still incomplete and contradictory. The aim of the present study was to ascertain the expression of BDKRB1 and BDKRB2 genes, as well as the level of B1R and B2R proteins in human gliomas, depending on the degree of malignancy. Additionally, representative kinin-dependent genes with altered expression were indicated. The expression profile of kinin-dependent genes was determined using oligonucleotide microarray technique. In addition, RT-qPCR was used to assess the expression level of selected differentiating genes. The location of kinin receptors in brain gliomas was assessed using immunohistochemical methods. The oligonucleotide microarray method was used to identify 12 mRNA IDs of kinin-related genes whose expression was upregulated or downregulated in gliomas of different grades. In immunohistochemically stained samples, the concentrations of BR1 and BR2 proteins, measured by optical density, were statistically significantly higher in grade G3 vs. G2 and G4 vs. G3. Increased expression of kinin receptors BDKRB1 and BDKRB2 in brain gliomas, depending on the degree of malignancy, suggests the involvement of kinins and their receptors in the disease's pathogenesis. Quantitative assessment of mRNA BDKRB1, PRKAR1A, MAP2K, and EGFR in patients with brain tumors may hold diagnostic and therapeutic significance.

项与 B1 receptor 相关的新闻（医药）

2023-06-08

·Science Daily

A new way to develop drugs without side effects

Have you ever wondered how drugs reach their targets and achieve their function within our bodies? If a drug molecule or a ligand is a message, an inbox is typically a receptor in the cell membrane. One such receptor involved in relaying molecular signals is a G protein-coupled receptor (GPCR). About one-third of existing drugs work by controlling the activation of this protein. Researchers now reveal a new way of activating GPCR by triggering shape changes in the intracellular region of the receptor. This new process can help researchers design drugs with fewer or no side effects. Have you ever wondered how drugs reach their targets and achieve their function within our bodies? If a drug molecule or a ligand is a message, an inbox is typically a receptor in the cell membrane. One such receptor involved in relaying molecular signals is a G protein-coupled receptor (GPCR). About one-third of existing drugs work by controlling the activation of this protein. Japanese researchers now reveal a new way of activating GPCR by triggering shape changes in the intracellular region of the receptor. This new process can help researchers design drugs with fewer or no side effects. If the cell membrane is like an Oreo cookie sandwich, GPCR is like a snake with seven segments traversing in and out of the cookie sandwich surface. The extracellular loops are the inbox for messages. When a message molecule binds to the extracellular side of the receptor, it triggers a shape change activating G proteins and the ß-arrestin protein attached to the intracellular side of the receptor. Like a molecular relay, the information passes downstream and affects various bodily processes. That is how we see, smell, and taste, which are sensations of light, smell, and taste messages. Adverse side effects ensue if drugs acting on GPCRs activate multiple signaling pathways rather than a specific target pathway. That is why drug development focuses on activating specific molecular signal pathways within cells. Activating the GPCR from inside the cell rather than outside the cell could be one way to achieve specificity. But until now, there was no evidence of direct activation of only the intracellular side of GPCRs without the initiations from the extracellular side. A team of researchers headed by Osamu Nureki, a professor at the University of Tokyo, and his lab, discovered a new receptor activation mode of a bone metabolism-related GPCR called human parathyroid hormone type 1 receptor (PTH1R) without signal transduction from the extracellular side. "Understanding the molecular mechanism will enable us to design optimal drugs," says Kazuhiro Kobayashi, a doctoral student and an author of the study. Such a drug offers "a promising treatment for osteoporosis." Kobayashi has been conducting research on bone formation in animal models since he was an undergrad. "Treatments for osteoporosis that target PTH1R require strict dosage, have administrative restrictions, and there aren't yet any better alternatives," he says. That motivated their team to look for better drug design strategies targeting the parathyroid hormone receptor. To understand function through structure, they used cryo-electron microscopy and revealed the 3D structure of the PTH1R and G protein bound to a message molecule. The team synthesized a non-peptide message molecule called PCO371 which binds to the intracellular region of the receptor and interacts directly with G protein subunits. In other words, PCO371 activates the receptor after entering the cell. The PCO371-bound PTH1R structure can directly and stably modulate the intracellular side of PTH1R. And because PCO371 activates only G protein and not ß-arrestin it does not cause side effects. This specificity of its binding and receptor activation mode makes it a suitable candidate for potential small-molecule-based drugs for class B1 GPCRs, like PTH1R, which currently lack oral administrative drug ligands. Such drugs would have reduced adverse effects and burdens on patients as they act on specific molecular pathways. The findings from this study will help "develop new drugs for disorders such as obesity, pain, osteoporosis, and neurological disorders." The study appears in the journal Nature.

2023-05-15

·EndPoints

Bayer cuts four programs amid a 'slow start' to the year

Bayer announced a handful of pipeline cuts in its quarterly earnings report last week, as CEO Werner Baumann revealed the quarter “came in soft” compared to last year’s performance. The culls include two Phase II programs, a BDKRB1 receptor antagonist for neuropathic pain, and runcaciguat, in development for chronic kidney disease. The BDKRB1 receptor plays a role in pain perception, and Bayer’s candidate, BAY 2395840, came out of a research alliance with Evotec. The company also said it’s discontinuing a Phase I program studying BAY 2395840 in endometriosis. Unlock this story instantly and join 168,600+ biopharma pros reading Endpoints daily — and it's free.

临床2期临床1期财报

2023-05-13

·GBIHealth

拜耳2023Q1 | 停止四项临床试验，处方药业务期待新品发力

点击蓝字GBIHealth关注我们SUBSCRIBE to us5月12日，拜耳公布2023年第一季度业绩报告，期内集团销售额与去年同期基本持平，达到143.89亿欧元（-1.1%）；净收益同比下降33.8%至21.78亿欧元。来源：拜耳财报各业务部门中，处方药事业部销售额为44.07亿欧元，同比下降3.1%。按区域划分，拜耳处方药业务在北美、拉美及欧洲/中东/非洲地区的销售额浮动不大，分别达到11.1亿欧元（+5.4%）、2.21亿欧元（+3.7%）和17.71亿欧元（-2.1%）；亚太地区销售额显著下降，同比缩减10.8%至13.05亿欧元。这一下降主要是由于中国带量采购政策（VBP）的影响；心血管领域药品拜瑞妥（利伐沙班）、拜新同（硝苯地平）受到的冲击尤为严重，销量分别同比下滑12.8%和23.9%。新冠疫情也对其在华开展处方药销售业务造成了一定的负面影响。拜耳指出，随着前列腺癌去势治疗药物诺倍戈（达罗他胺）、肾病领域新药可申达（非奈利酮）的快速放量，以及放射学业务的持续强劲增长，处方药业务仍将显著受益。来源：拜耳财报与此同时，健康消费品事业部销售额持续增长，达到15.73亿欧元（+4.1%），主要受益于过敏、感冒以及皮肤病领域产品的推动。按区域划分，北美、拉美及欧洲/中东/非洲地区业务均有不同程度增长，分别达到6.12亿欧元（+1.2%）、2.01亿欧元（+16.1%）和5.16亿欧元（+5.7%）；亚太地区则同比下降1.2%至2.44亿欧元。人员调整方面，拜耳公司监事会任命Bill Anderson为拜耳公司首席执行官（CEO），自2023年6月1日起生效；Bill Anderson曾任罗氏制药CEO，2023年4月1日加入拜耳，担任管理委员会成员。拜耳现任CEO Werner Baumann将于2023年5月底退休。根据财报电话会，拜耳在第一季度还对管线作出了调整。涉及三款产品的四项临床试验在此期间停止，包括：缓激肽B1（BDKRB1）受体拮抗剂（研发代号：BAY 2395840）的I期研究及其治疗神经性疼痛的II期研究，P2X4拮抗剂（研发代号：BAY 1797）的I期研究，以及可溶性鸟苷酸环化酶（sGC）激动剂Runcaciguat（研发代号：BAY 1101042）治疗慢性肾疾病的II期研究。根据公开信息，BAY-2395840和BAY-1797被认为来自拜耳与德国Evotec自2012年合作的多靶点研究；Runcaciguat则来自拜耳内部研发平台。有奖调研点击阅读原文立即参与活动

财报高管变更带量采购临床1期