PI3Kδ的选择性抑制剂CPL302-253作为吸入治疗和预防哮喘的候选药物的临床前表征
2021/04/23
摘要
支气管哮喘是一种常见的慢性炎症性疾病。虽然有有效的哮喘治疗，但部分哮喘人群对这些治疗方案没有反应。在这项工作中，我们提出一种PI3Kδ的选择性抑制剂CPL302-253分子的开发结果。该分子旨在作为哮喘治疗中干粉吸入的临床前候选药物。我们进行的研究表明，该分子是安全有效的PI3Kδ抑制剂，可以影响许多免疫功能。我们开发了一个15天HDM诱导的哮喘小鼠模型，显示CPL302-253能够阻断体内哮喘的炎症发展过程。
Preclinical characterization of CPL302-253, a selective inhibitor of PI3Kδ, as the candidate for the inhalatory treatment and prevention of Asthma
Paweł Gunerka, Kamila Gala, Martyna Banach, Jakub Dominowski, Joanna Hucz-Kalitowska, Krzysztof Mulewski, Agnes Hajnal, Endre G Mikus, Damian Smuga, Marcin Zagozda , Krzysztof Dubiel, Jerzy Pieczykolan, Beata M Zygmunt, Maciej Wieczorek
Abstract
Asthma is a common chronic inflammatory disease. Although effective asthma therapies are available, part of asthmatic population do not respond to these treatment options. In this work we present the result of development of CPL302-253 molecule, a selective PI3Kδ inhibitor. This molecule is intended to be a preclinical candidate for dry powder inhalation in asthma treatment. Studies we performed showed that this molecule is safe and effective PI3Kδ inhibitor that can impact many immune functions. We developed a short, 15-day HDM induced asthma mouse model, in which we showed that CPL302-253 is able to block inflammatory processes leading to asthma development in vivo.
支气管哮喘是一种常见的慢性炎症性疾病。虽然有有效的哮喘治疗，但部分哮喘人群对这些治疗方案没有反应。在这项工作中，我们提出一种PI3Kδ的选择性抑制剂CPL302-253分子的开发结果。该分子旨在作为哮喘治疗中干粉吸入的临床前候选药物。我们进行的研究表明，该分子是安全有效的PI3Kδ抑制剂，可以影响许多免疫功能。我们开发了一个15天HDM诱导的哮喘小鼠模型，显示CPL302-253能够阻断体内哮喘的炎症发展过程。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(PLoS One . 2020 Jul 23;15(7):e0236159. doi: 10.1371/journal.pone.0236159 .)
(PLoS One . 2020 Jul 23;15(7):e0236159. doi: 10.1371/journal.pone.0236159 .)
Preclinical characterization of CPL302-253, a selective inhibitor of PI3Kδ, as the candidate for the inhalatory treatment and prevention of Asthma
Paweł Gunerka, Kamila Gala, Martyna Banach, Jakub Dominowski, Joanna Hucz-Kalitowska, Krzysztof Mulewski, Agnes Hajnal, Endre G Mikus, Damian Smuga, Marcin Zagozda , Krzysztof Dubiel, Jerzy Pieczykolan, Beata M Zygmunt, Maciej Wieczorek
Abstract
Asthma is a common chronic inflammatory disease. Although effective asthma therapies are available, part of asthmatic population do not respond to these treatment options. In this work we present the result of development of CPL302-253 molecule, a selective PI3Kδ inhibitor. This molecule is intended to be a preclinical candidate for dry powder inhalation in asthma treatment. Studies we performed showed that this molecule is safe and effective PI3Kδ inhibitor that can impact many immune functions. We developed a short, 15-day HDM induced asthma mouse model, in which we showed that CPL302-253 is able to block inflammatory processes leading to asthma development in vivo.
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肺功能波动模式揭示与2型炎症无关的哮喘与COPD表型
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严重中性粒细胞性哮喘患者痰中ACE2，TMPRSS2和FURIN基因表达
