Tz-Thalidomide

Tz-Thalidomide is a tetrazine-tagged Thalidomide (HY-14658), an E3 ligase ligand. Tz-Thalidomide self-assembles with TCO-labeled target protein inhibitors, forming a CLIP-TAC (targeted protein degradation chimera) via click chemistry. This chimera recruits the E3 ubiquitin ligase CRBN to the target protein, thereby inducing ubiquitination and subsequent degradation of the target protein. When used in combination with JQ1-TCO (HY-148864), Tz-Thalidomide induces concentration-dependent degradation of BRD4 in cells. When combined with ERK-targeting protein inhibitors, Tz-Thalidomide induces degradation of ERK1/2 in cells. Tz-Thalidomide can be used in cancer-related research^[1]. IC50 & Target:46.25 μM (BRD4-1), 62.55 μM (BRD4-2)^[1] In Vitro:Tz-Thalidomide exhibits extremely weak binding to the bromodomains of BRD4-1 and BRD4-2, with IC₅₀ values of 46.25 μM and 62.55 μM, respectively^[1].
Tz-Thalidomide (30 μM; 30 min) exhibits extremely weak inhibitory activity against ERK2, showing only 46% inhibition at a concentration of 30 μM^[1].
Combined with JQ1-TCO, Tz-Thalidomide (0.1-10 μM; 18 h) induces concentration-dependent degradation of BRD4 in HeLa cells, with complete degradation achieved at concentrations of 10 μM and 3 μM after 18 h of incubation^[1].
Combination treatment with Tz-Thalidomide (10 μM; 1-24 h) and JQ1-TCO induces time-dependent degradation of BRD4 in HeLa cells, with complete degradation observable after 24 h of incubation^[1].
Combination treatment with Tz-Thalidomide (10 μM; 1-24 h) and Probe 1 induces time-dependent degradation of ERK1/2 in A375 cells, with complete degradation observable after 16 h of incubation^[1].