Ikaros family zinc finger protein 2 (IKZF2) (IKZF2)

Ikaros family zinc finger protein 2 (IKZF2), also known as Helios, is a transcription factor essential for maintaining the stability and suppressive function of regulatory T-cells (Tregs). In the context of oncology, IKZF2 is often overexpressed in certain leukemias and solid tumors, where it contributes to an immunosuppressive tumor microenvironment by preventing Treg reprogramming into effector-like cells. The therapeutic strategy involves using 'molecular glue' degraders that facilitate a neo-substrate interaction between IKZF2 and the Cereblon (CRBN) E3 ubiquitin ligase complex. This recruitment leads to the polyubiquitination and subsequent proteasomal degradation of IKZF2. By depleting IKZF2, these drugs aim to destabilize intratumoral Tregs and enhance the anti-tumor immune response, making it a promising target for cancer immunotherapy.

Other names

HeliosZinc finger protein HeliosANF1A2Ikaros family zinc finger 2ZNFN1A2

Targeted protein degradation via molecular glue recruitment of the CRL4-CRBN E3 ubiquitin ligase complex