Katsuya, Ken; Oikawa, Daisuke; Iio, Kiyosei; Obika, Shingo; Hori, Yuji; Urashima, Toshiki; Ayukawa, Kumiko; Tokunaga, Fuminori published the artcile< Small-molecule inhibitors of linear ubiquitin chain assembly complex (LUBAC), HOIPINs, suppress NF-kB signaling>, Synthetic Route of 329214-79-1, the main research area is LUBAC HOIPIN nuclear factor signalling; Cytokine; Enzyme inhibitor; Inflammation; NF-κB; Ubiquitin.
Nuclear factor-kB (NF-kB) is a crucial transcription factor family involved in the regulation of immune and inflammatory responses and cell survival. The linear ubiquitin chain assembly complex (LUBAC), composed of the HOIL-1L, HOIP, and SHARPIN subunits, specifically generates Met1-linked linear ubiquitin chains through the ubiquitin ligase activity in HOIP, and activates the NF-kB pathway. We recently identified a chem. inhibitor of LUBAC, which we named HOIPIN-1 (HOIP inhibitor-1). To improve the potency of HOIPIN-1, we synthesized 7 derivatives (HOIPIN-2~8), and analyzed their effects on LUBAC and NF-kB activation. Among them, HOIPIN-8 suppressed the linear ubiquitination activity by recombinant LUBAC at an IC50 value of 11 nM, corresponding to a 255-fold increase over that of HOIPIN-1. Furthermore, as compared with HOIPIN-1, HOIPIN-8 showed 10-fold and 4-fold enhanced inhibitory activities on LUBAC- and TNF-a-induced NF-kB activation resp., without cytotoxicity. These results indicated that HOIPIN-8 is a powerful tool to explore the physiol. functions of LUBAC.
Biochemical and Biophysical Research Communications published new progress about Animal gene, ICAM1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 329214-79-1 belongs to class pyridine-derivatives, and the molecular formula is C11H16BNO2, Synthetic Route of 329214-79-1.