BI 1015550 is an orally active inhibitor of PDE4B with an IC50 value of 7.2 nM. BI 1015550 has good safety and potential applications in inflammation, allergic diseases, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD)[1][2].
BI 1015550 在人 PBMCs 中抑制脂多糖 (Lipopolysaccharides，D1056) 诱导的 TNF-α 的释放，植物血凝素 P (Ptohemagglutinin P，N7038A) 诱导的 IL-2 的释放，IC50 值分别为 35 nM 和 9 nM[2]。
BI 1015550 在大鼠全血中抑制 TNF-α 的释放，IC50 值为 91 nM[2]。
BI 1015550 (Example 2) (0、0.3、1.0 和 3.0 mg/kg；口服；单剂量) 在 1.0 mg/kg 时弱化了大鼠的肠道转运，但不显著影响体重[1]。
BI 1015550 能预防大鼠肺组织的炎症，ED50 值为 0.1 mg/kg[1]。
BI 1015550 (0.01、0.1 和 1.0 mg/kg；口服；单剂量) 在小鼠血浆中以剂量依赖性方式减少了脂多糖 (Lipopolysaccharides，D1056) 诱导的 TNF-α 的释放[2]。
BI 1015550 (0.1、0.3 和 1.0 mg/kg；口服；单剂量) 抑制脂多糖诱导的中性粒细胞进入雄性 Suncus Murinus 和 Wistar 大鼠支气管肺泡灌洗液[2]。
BI 1015550 (2.5 mg/kg 和 12.5 mg/kg；口服；一天 2 次持续 6 天) 有效改善了博来霉素 (Bleomycin，5) 对小鼠的损害[2]。
| Animal Model: | Rats[1]. |
| Dosage: | 0, 0.3, 1.0 and 3.0 mg/kg. |
| Administration: | Oral gavage; single dose. |
| Result: | Had minimal toxic and side effects on the intestines and stomach of rats, demonstrating biosafety. |
| Animal Model: | Male Suncus Murinus and Wistar rats; mice[2]. |
| Dosage: | 0.01, 0.1, 0.3, 1.0, 2.5 or 12.5 mg/kg. |
| Administration: | Oral gavage; single dose or twice daily for 6 days. |
| Result: | Effectively improved inflammation in lung tissue and reduced the pro-inflammatory factor TNF-α release. |
[1]. Pouzet P A, et al. Piperidino-didrothienopyrimidine sulfoxides and their use for treating COPD and asthma. United States. US9150586.
[2]. Herrmann FE, et al. BI 1015550 is a PDE4B Inhibitor and a Clinical Drug Candidate for the Oral Treatment of Idiopathic Pulmonary Fibrosis. Front Pharmacol. 2022 Apr 20;13:838449.