REDX08608: A Potent and Selective BTK Inhibitor Effective Against Wild-Type and Mutant C481S BTK in Oncology

3 June 2024
The study introduces REDX08608, a novel BTK inhibitor developed to address resistance mechanisms in B-cell malignancies. This compound is potent and selective, capable of inhibiting both wild-type and C481S mutated BTK, which is crucial for overcoming resistance seen in patients with CLL progression after ibrutinib treatment. REDX08608 demonstrates nanomolar binding affinity and potency in various assays and effectively inhibits BTK signaling and growth in cell lines reliant on the BTK pathway, including primary CLL cells. It also suppresses B-cell activation in human blood and PBMCs at nanomolar concentrations.

The compound has been shown to be highly selective against a panel of 468 kinases, with significant selectivity against Tec and Src kinase family members and EGFR. REDX08608 has undergone comprehensive DMPK profiling, revealing acceptable metabolic and plasma stability across different species. It does not activate PXR or exhibit time-dependent inhibition, and it has a favorable profile for cytochrome P450 inhibition. The compound has demonstrated good exposure, oral bioavailability, and half-life in preclinical models, with dose linearity assessed in mice, rats, and dogs.

The study concludes that REDX08608 is a promising reversible BTK inhibitor with potential efficacy in targeting both wild-type and resistant forms of BTK in lymphoma cell lines. The disclosures section indicates that multiple authors are employed by Redx Oncology Ltd - Redx Pharma Plc, with some also having research funding connections to other pharmaceutical companies.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

图形用户界面, 文本, 应用程序, 电子邮件

描述已自动生成

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

图形用户界面, 文本, 应用程序, 电子邮件

描述已自动生成

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

图片包含 应用程序

描述已自动生成

Click on the image below to go directly to the Translational Medicine search interface.

图形用户界面, 文本, 应用程序, 电子邮件

描述已自动生成