PT-179 is an orthogonal Thalidomide derivative that targets cereblon without causing off-target degradation effects. PT-179 is able to specifically bind CRBN, form a ternary complex with a target protein fused to a zinc finger (ZF) degron, and mediate the degradation of the tagged protein. For example, PT-179 binds to the ubiquitin ligase substrate receptor cereblon by forming a complex with SD40 and efficiently degrades proteins N- or C-terminally fused to SD40 or SD36 (DC50 for eGFP: 4.5 nM and 14.3 nM). PT-179 can be used to develop compact protein degradation tagging platforms.
SD40 is a degradation tag specific for PT-179. PT-179 (1-10 μM; 24 h) can induce eGFP degradation in HEK293T cells. The higher the evolution degree of the degron variant, the stronger the degradation efficiency of the corresponding tagged protein[1].
References:
[1]. Mercer JAM, et al. Continuous evolution of compact protein degradation tags regulated by selective molecular glues. Science. 2024 Mar 15;383(6688):eadk4422.