E3 Ligase Ligand-Linker Conjugates 19

E3 Ligase Ligand-Linker Conjugates 19 is a degron-linker. The PROTAC linker is bound lo at least one targeting ligand.

Signaling Pathways >> PROTAC >> E3 Ligase Ligand-Linker Conjugate

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

Research Areas >> Cancer

E3 Ligase Ligand-Linker Conjugates 19 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]. E3 Ligase Ligand-Linker Conjugates 19 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].

[1]. Zhou B, et al. Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins withPicomolar Cellular Potencies and Capable of Achieving Tumor Regression. J Med Chem. 2017 Mar 24.

[2]. James Bradner, et al. Methods to induce targeted protein degradation through bifunctional molecules. WO 2017024317 A2.

(+)-JQ1 | GSK126 | Tazemetostat (EPZ-6438) | Birabresib (OTX015) | A 485 | Curcumin | ARV-771 | ARV-825 | I-BET762 | BI 2536 | GSK343 | C646 | 3-Deazaneplanocin A (hydrochloride) | I-BET151 | 666-15