LZ-07 is an IRAK4 PROTAC degrader (DC50 = 1.14 nM), that, upon degradation of IRAK4, significantly inhibits the expression of cytokines such as IL-6, IL-1β, TNF-α, and IL-10. It is applicable in research related to autoimmune diseases.

LZ-07 exhibits significant degradation activity in the THP-1 cell line, achieving over 65% degradation at 10 nM and exceeding 75% at 100 nM within 16 hours. In DOHH2 and TMD8 cells, LZ-07 shows dose-dependent IRAK4 degradation, with DC50 values of 1.14 nM and 2.70 nM, respectively, over a concentration range of 0.3-300 nM within 16 hours. At 50 nM, LZ-07 induces rapid and substantial degradation within 4 hours, reaching maximum degradation (Dmax = 91%) at 16 hours in TMD8 cells, and quickly degrades IRAK4 in DOHH2 cells. At a concentration of 30 nM over 8 hours, LZ-07 mediates IRAK4 degradation via the ubiquitin-proteasome system, depending on its interaction with IRAK and CRBN. Additionally, LZ-07 exhibits excellent inhibitory effects on four key inflammatory cytokines (IL-6, IL-10, IL-1β, and TNF-α) in LPS (100 ng/mL) stimulated PBMCs at concentrations between 3.9-7.6 nM over 2 hours.