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Pliant Therapeutics：推进纤维化疾病的药物开发计划
Pliant Therapeutics 是一家生物制药公司，致力于开发纤维化疾病的创新疗法。该公司的使命是通过推进针对纤维化相关特定途径和机制的药物开发计划，改善患有这些衰弱病症的患者的生活。
纤维化是一个复杂的过程，涉及疤痕组织在全身各器官和组织中的积累。这会导致器官功能障碍、活动能力受损，严重时甚至会导致死亡。纤维化疾病影响着全世界数百万人，包括肺纤维化、肝硬化、肾脏疾病和系统性硬化症患者。
Pliant Therapeutics 的药物开发方法侧重于抑制整合素和 TGF-β 通路。整合素是细胞表面受体，在细胞粘附和信号传导中起着关键作用。它们还参与纤维化过程中疤痕组织的形成。通过使用特定抑制剂靶向整合素，Pliant 旨在预防或减少受影响组织的纤维化。
TGF-β通路是 Pliant 药物开发计划的另一个关键目标。 TGF-β 是一种调节许多细胞过程的细胞因子，包括细胞生长和分化。它还通过刺激胶原蛋白和其他细胞外基质蛋白的产生，在促进纤维化方面发挥重要作用。通过选择性地抑制这一途径，Pliant 希望减少或逆转受影响组织的纤维化变化。
Pliant 有几个正在进行的药物开发计划，旨在使用其称为“智能肌成纤维细胞抑制剂”(SMI) 的专有平台技术治疗不同类型的纤维化疾病。 SMI 是一种小分子，旨在选择性地抑制肌成纤维细胞——负责在纤维化过程中产生过量胶原蛋白的细胞——而不影响其他细胞或组织。
其中一个项目针对特发性肺纤维化 (IPF)，这是一种慢性肺病，其特征是肺组织进行性瘢痕形成，随着时间的推移导致呼吸衰竭。 Pliant 的主要候选药物 PLN-74809 作为一种 SMI 抑制剂，在临床前研究中显示出可喜的结果，该抑制剂靶向 IPF 肺内特别发现的肌成纤维细胞，同时保留健康的肺细胞。
另一个项目针对由非酒精性脂肪性肝炎 (NASH) 引起的肝硬化，它影响了全世界数百万人，这主要是由于不健康的生活方式选择，如不良的饮食习惯导致与肥胖相关的健康问题，如 2 型糖尿病等。这种情况最终会导致肝组织内形成疤痕，导致它随着时间的推移无法正常运作，如果不及时治疗会导致肝功能衰竭。该公司的主要候选药物 PLN-1474 作为一种 SMI 抑制剂，已显示出令人鼓舞的结果，该抑制剂针对在 NASH 肝脏中特别发现的肌成纤维细胞，同时保留健康的肝细胞。
除了这些项目外，Pliant therapetics 还正在进行研究工作，重点是开发治疗系统性硬化症、糖尿病肾病、射血分数保留的心力衰竭 (HFpEF) 等。
总的来说，Pliant Therapeutics 开发针对与纤维化有关的特定途径的药物的创新方法对改善多种适应症的患者结果具有很大的希望。凭借其专有平台技术，SMI 显示出在不影响健康细胞/组织的情况下选择性抑制肌成纤维细胞的巨大潜力，以及强大的临床前数据支持其对各种类型纤维化的功效；看来我们很快就会看到这家公司更令人兴奋的发展！
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