Bifunctional degrader molecules, also called proteolysis-targeting chimeras (PROTACs), are a new modality of chemical tools and potential therapeutics to understand and treat human disease. A required PROTAC component is a ligand binding to an E3 ubiquitin ligase, which is then joined to another ligand binding to a protein to be degraded via the ubiquitin–proteasome system. The advent of nonpeptidic small-molecule E3 ligase ligands revolutionized the field and ushered in the design of drug-like PROTACs with potent and selective degradation activity.
PROTAC (Proteolysis-Targeting Chimeras) is a promising approach in drug discovery that involves the use of small molecules to target specific proteins for degradation by the cellular machinery.
Wee1 protein is the most well-known Wee protein, and Wee1 protein kinases are members of the serine/threonine family and are highly conserved in evolution and are abundantly present in many eukaryotes and are very active in the S and G2 phases of the cell cycle. Wee1 protein kinase is a key regulatory center in DNA replication, chromosomal concentration, and histone transcription. These biological behavioral abnormalities can lead to genomic instability and cause malignant tumors, but inhibition or down-regulation of Wee1 protein kinase expression in malignant tumors can trigger mitotic catastrophe and apoptosis leads to tumor cell death. It has now been found that the expression of Wee1 is up-regulated in many cancers, and it has been clinically found that treatment with an inhibitor of Wee1 can effectively improve the occurrence and development of cancer. At present, many companies have deployed this target, and some have progressed to the clinical stage. Some Wee1 inhibitors under development include Adavosertib(ADZ1775), Azenosertib, ZNL-06-096, Debio-0123 and SGR-3515. Chemenu has been working to develop more compounds for drug discovery. Here are the building blocks we can provide.