KB02-JQ1 is a Highly Potent and Selective PROTAC BRD4 Degrader
DDB1-CUL4-associated protein 16 (DCAF16) is a 216 aa protein that is highly conserved across mammals, but absent from rodents. The DCAF16 protein has eight cysteine residues, including a cluster of four cysteines between amino acids 173-179. Especially, DCAF16 is a substrate recognition component of CUL4-DDB1 E3 ubiquitin ligases. DCAF16...
MS432 is a Highly Selective PROTAC Degrader for MEK1 and MEK2
Chemical induced protein knockdown via the proteolysis targeting chimera (PROTAC) technology is a promising approach to target dysregulated proteins. Moreover, MEK1/2 proteins are the only RAF substrates. MEK1/2 proteins are the crucial “gatekeepers” of ERK activity. The classic RAS-RAF-MEK-ERK signaling pathway is common in mammals, plays critical roles in...
SD-36 is a Selective PROTAC STAT3 Degrader
Proteolysis targeting chimera (PROTAC) technology has been a type of therapeutics that induces targeted protein degradation. Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. In this study, Longchuan Bai, et al developed a potent and specific PROTAC degrader of STAT3 and evaluate its...
MD-224 is a First-in-Class and Highly Potent PROTAC Degrader of MDM2
As previously introduced, the tumor suppressor p53 plays a critical role in the prevention of tumor development. While human, murine double minute 2 (MDM2) protein is a primary endogenous cellular inhibitor of the tumor suppressor p53. And it has been pursued as a promising cancer therapeutic target. A study...
GMB-475, a BCR-ABL1 Inhibitor Based on PROTAC, Has Potential to Overcome BCR-ABL1-Dependent Drug Resistance
Chronic myeloid leukemia is a myeloproliferative disorder characterized by the presence of the oncogenic fusion protein BCR-ABL1. ABL1, one of the fusion partners in the BCR-ABL1 protein, contains an allosteric myristoylation binding site. Especially, the proteolysis targeting chimera (PROTAC) technology provides a unique toolkit for probing the non-kinase roles...
ARV-825 is a PROTAC Degrader of BRD4 with Profound Anti-Leukemic Effect
BRD4 (Bromodomain-containing protein 4) belongs to the BET family, which also contains BRD2, BRD3, and BRDT. BRD4 has two bromodomains to recognize acetylated lysine residues. They are BD1 and BD2. It also contains an extended C-terminal domain. The latter interacts with P-TEFb and RNA polymerase II to promote gene...
BSJ-03-123, a Degrader with Proteome-wide Selectivity for CDK6 (PROTAC)
A study from Matthias Brand reported a novel phthalimide-based degrader BSJ-03-123. This compound exploits protein-interface determinants to achieve proteome-wide selectivity for the degradation of cyclin-dependent kinase 6 (CDK6). Notably, CDK6 degradation targets a selective dependency of acute myeloid leukemia cells. Cyclin-dependent kinases (CDKs) participate in regulating fundamental cellular processes...