Thalidomide-O-amido-C4-NH2

Thalidomide-O-amido-C4-NH2 (Cereblon Ligand-Linker Conjugates 6), a synthesized E3 ligase ligand-linker conjugate that incorporates the Thalidomide based cereblon ligand and a linker, can be used in the synthesis of PROTACs^[1]. In Vitro: Thalidomide-O-amido-C4-NH2 is an amine intermediate (Compound 41), which can be used as is a heterobifunctional PROTAC BET degrader. The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic “readers” and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-molecule BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation^[1]. Thalidomide-O-amido-C4-NH2 is a degron-linker (refer to Compound DL6-TL). Degron-linker-targeting ligand, wherein the linker is covalently bound lo at least one degron and at least one targeting ligand, the degron is a compound capable of binding to an ubiquitin ligase such as an E3 ubiquitin ligase (e g, cereblon), and the targeting ligand is capable of binding to the targeted protein (s)^[2].