CCW 28-3 is a BRD4 PROTAC degrader. CCW 28-3 recruits RNF4 to BRD4, inducing RNF4 -dependent ubiquitination and proteasomal degradation of BRD4. CCW 28-3 can be used in breast cancer-related research [1] [2]. (Pink: BRD4 ligand; Blue: RNF4 ligand; Black: linker ).
In Vitro, CCW 28-3 (30 min) potently inhibits the labeling of purified recombinant human RNF4 by IA-rhodamine in gel-based competitive ABPP assays, with an IC50 of 0.54 μM[1]. CCW 28-3 (1 h) degrades BRD4 in 231MFP breast cancer cells in a time- and dose-dependent manner, and this degradation is dependent on the proteasome and RNF4[1]. CCW 28-3 (10 μM; 1.5 h) achieves approximately 30% target binding rate to overexpressed RNF4 in HEK293T cells[1]. CCW 28-3 potently inhibits purified RNF4 with an IC50 of 0.54 μM[2].
References:
[1]. Ward CC, et al. Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications. ACS chemical biology. 2019 Nov 15;14(11):2430-2440.
[2]. Kiely-Collins H, et al. The role of reversible and irreversible covalent chemistry in targeted protein degradation. Cell Chem Biol. 2021 Jul 15;28(7):952-968.
In Vitro, CCW 28-3 (30 min) potently inhibits the labeling of purified recombinant human RNF4 by IA-rhodamine in gel-based competitive ABPP assays, with an IC50 of 0.54 μM[1]. CCW 28-3 (1 h) degrades BRD4 in 231MFP breast cancer cells in a time- and dose-dependent manner, and this degradation is dependent on the proteasome and RNF4[1]. CCW 28-3 (10 μM; 1.5 h) achieves approximately 30% target binding rate to overexpressed RNF4 in HEK293T cells[1]. CCW 28-3 potently inhibits purified RNF4 with an IC50 of 0.54 μM[2].
References:
[1]. Ward CC, et al. Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications. ACS chemical biology. 2019 Nov 15;14(11):2430-2440.
[2]. Kiely-Collins H, et al. The role of reversible and irreversible covalent chemistry in targeted protein degradation. Cell Chem Biol. 2021 Jul 15;28(7):952-968.