Definition

An orally bioavailable protein degrader of the transcription factors Ikaros (Ikaros family zinc finger protein 1; IKZF1) and Aiolos (Ikaros family zinc finger protein 3; IKZF3), with potential immunomodulating and antineoplastic activities. Upon oral administration, IKZF1/IKZF3 protein degrader GLB-002 modulates the E3 (ubiquitin) ligase and targets IKZF1 and IKZF3 for ubiquitination, and induces proteasome-mediated degradation of IKZF1 and IKZF3. This reduces the levels of these transcription factors, which are transcriptional repressors in T cells, and modulates the activity of the immune system. This also leads to the downregulation of other proteins, including interferon regulatory factor 4 (IRF4), which may result in apoptosis and the inhibition of tumor cell proliferation. IKZF1 and IKZF3 play a key role in B- and T-cell differentiation. IRF4, overexpressed in certain malignancies, is a transcription factor and key regulator of multiple genes controlling tumor cell survival.