Page 16 - F. Cell biology

[F. Cell biology-8]

Identification of small molecules that can inhibit necroptotic

cell death

Su Bin Sin¹, Young Sik Cho¹˙*

¹College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea

Programmed necrosis (necroptosis) has been recognized as a specialized and regulated necrosis that is aroused
when apoptosis is defective. Initially, it is known to play a beneficial significance in innate immune response to viral
infection that can evade immune surveillance. Now, it has been emerging as the strategy to overcome the cancers

with acquired drug resistance. In contrast, it has been proposed that necroptotic cell death is pathologically

associated with ischemic brain damage and degenerative diseases. Here, as an effort to discover hits that can
selectively inhibit necroptotic cell death, we screened in-house and in silico chemical libraries in a cell based assay.
Eventually, 7 hits were identified from in-house chemical library while 2 hits were from modeling data. Mostly, hits

exhibited less protective activity from TNF- and zVAD-mediated necroptosis than a reference compound Nec-1.
Interestingly, a few of hits had preferential protective effects on zVAD or TNFα while Nec-1 exhibited similar IC50

against zVAD or TNF, suggesting that deduced chemicals can discriminate signaling pathways leading to receptor
or nonreceptor-mediated necroptotic cell death.