SRI-37240

SRI-37240 is a potent premature termination codons (PTCs) inhibitor. SRI-37240 suppresses CFTR nonsense mutations. SRI-37240 alters cellular translation termination at PTCs in HEK293T cells. SRI-37240 can also restore CFTR function in primary bronchial epithelial cells when combination with G418[1].

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

Research Areas >> Inflammation/Immunology

Premature termination codons, CFTR[1]

SRI-37240 (1, 3, 10 and 30 µM; 48 h) induces concentration-dependent increases in CFTR-dependent (Forskolin-stimulated and sensitive to the inhibitor CFTRInh-172) chloride conductance[1]. SRI-37240 (10 µM; 72 h) significantly increases the amount of full-length, fully glycosylated form of CFTR protein, and the unprocessed, immature form of full-length CFTR protein in 16HBEge cells when co-treated with G418 (100 µM)[1]. SRI-37240 (10 µM; 24 h) alters cellular translation termination at PTCs in HEK293T cells, also increases global densities of ribosomes at normal stop codons without affecting densities of ribosomes in 3-UTRs[1]. SRI-37240 (10 µM; 72 h) restores CFTR function in primary bronchial epithelial cells when combination with G418[1]. Western Blot Analysis[1] Cell Line: CFTR-G542X 16HBEge Concentration: 10 µM Incubation Time: 24 h Result: Significantly increased the amount of Band C CFTR protein, which represents the full-length, fully glycosylated form of CFTR and Band B, which represents the unprocessed, immature form of full-length CFTR protein when combined with G418 (100 µM).

[1]. Sharma J, et al. A small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion. Nat Commun. 2021 Jul 16;12(1):4358.