CFTR activator 1

CFTR activator 1 is a potent and selective CFTR activator, with an EC50 of 23 nM. CFTR activator 1 can be used to ameliorate dry eye disease[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> CFTR

Research Areas >> Inflammation/Immunology

EC50: 23 nM (CFTR)[1]

CFTR activator 1 (compound 16d) (30 nM-10 μM) 在存在 50 nM Forskolin 的情况下有效激活表达人 CFTR 的 FRT 细胞中的 CFTR 氯离子通道，EC50 值为 342 nM[1]。 CFTR activator 1 (30 μM; pretreated for 10 min or 5 min) 不影响表达人 ANO1 的 FRT 细胞和表达卤化物传感器 YFP-F46L/H148Q/I152L 的 LN215 细胞中 ANO1 和 VRAC 的通道活性[1]。 CFTR activator 1 (30 μM; 10 min) 略微增加 CHO-K1 细胞中 cAMP 水平[1]。 CFTR activator 1 (30 μM; 48 h) 不影响 CorE 和 ConjE 的细胞活力[1]。

CFTR activator 1 (compound 16d) (2060 μM; 5 μL of eye drops; 3 times a day for 10 d) 在干眼病 (DED) 小鼠模型中增强泪液分泌并改善角膜侵蚀。CFTR activator 1 降低 DED 小鼠角膜和结膜中促炎细胞因子 (包括 IL-1β、IL-17、TNF-α 和 MMP2) 的 mRNA 表达[1]。 CFTR activator 1 (0.1 mg/eye; 滴眼液单次局部滴注) 在雄性新西兰白兔的 CFTR 表达靶组织（角膜和结膜）中分布良好，维持时间长，全身暴露几乎可以忽略不计[1]。 Animal Model: Eight weeks old female C57BL/6J mice were injected Scopolamine hydrobromide[1] Dosage: 2060 μM, 5 μL, and maintained for 30 s Administration: Eye drop application was done in both eyes, three times a day (11:00 am, 2:00 pm, 5:00 pm) for 10 days Result: Enhanced tear secretion and improved corneal erosion. Reduced mRNA expression of pro-inflammatory cytokines including IL-1β, IL-17, and TNF-α and MMP2 in cornea and conjunctiva.

[1]. Kim BY, et, al. Synthetic Strategies for Improving Solubility: Optimization of Novel Pyrazolo[1,5- a]pyrimidine CFTR Activator That Ameliorates Dry Eye Disease. J Med Chem. 2023 Jan 12;66(1):413-434.