SW044248 is a non-canonical topoisomerase I inhibitor, and selectively toxic for certain non-small cell lung cancer (NSCLC) cell lines.
SW044248 is a non-canonical Top1 inhibitor, and is selectively toxic for certain NSCLC cell lines. SW044248 shows no effect on Top2. SW044248 (2, 5, 10 uM) rapidly inhibits transcription, translation and DNA synthesis in sensitive cells (HCC4017 and H292 cells) but not insensitive cells (HBEC30KT cells and HCC44 cells). SW044248 (10 uM) rapidly activates the integrated stress response through kinases GCN2 and PKR. The inhibition of Top1 in HCC4017 cells is helpful to the toxicity of SW044248. SW044248 (5, 10 uM) shows no effect on HBEC30KT and HCC44 cell lines due to the up-regulation of p21CDKN1A[1]. SW044248 is selectively toxic in 18/74 NSCLC lines[2].
References:
[1]. Zubovych IO, et al. A Novel Inhibitor of Topoisomerase I Is Selectively Toxic for a Subset of Non-Small Cell Lung Cancer Cell Lines. Mol Cancer Ther. 2016 Jan;15(1):23-36.
[2]. Kim HS, et al. Systematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer. Cell. 2013 Oct 24;155(3):552-66.