Qingping Zeng

TL;DR: Results demonstrate that blockade of XBP1 splicing by inhibition of IRE1α endoribonuclease domain is a potential therapeutic option in MM.

TL;DR: It is shown that inhibition of IRE1’s RNase activity attenuates autocrine and paracrine signaling of pro-tumorigenic cytokines and synergizes with paclitaxel to confer potent anti-t tumor effects in TNBC.

TL;DR: It is reported that an IRE1α RNase-specific inhibitor, MKC8866, strongly inhibits prostate cancer (PCa) tumor growth as monotherapy in multiple preclinical models in mice and shows synergistic antitumor effects with current PCa drugs.

TL;DR: It is shown that oncogenic MYC regulates the inositol-requiring enzyme 1/X-box binding protein 1 (XBP1) branch of the UPR in breast cancer via multiple mechanisms, and it is demonstrated that XBP1 is a synthetic lethal partner of MYC.

TL;DR: Structural activity studies and mutational analysis of contact residues define the optimal chemical space of inhibitors and validate the inhibitor binding site, laying the foundation for understanding both the biochemical and cellular functions of IRE1α using small molecule inhibitors and suggest new avenues for inhibitor design.