PROTAC BTK Degrader-1

PROTAC BTK Degrader-1, a powerful, selective, and orally bioavailable degrader of PROTAC BTK, demonstrates effective reduction in BTK protein levels and tumor suppression. It exhibits IC50 values of 34.51 nM for BTK WT and 64.56 nM for BTK-481S, highlighting its potency and efficacy in targeting and diminishing BTK protein abundance [1].

PROTAC BTK Degrader-11 is a PROTAC degrader that targets and degrades BTK with a DC50 of 1.7 nM. It is utilized in oncological research.

PROTAC BTK Degrader-12 (EXAMPLE 19) is a PROTAC-based BTK degrader, featuring a structure where the BTK ligand and linker are highlighted in pink and black, the linker in black, and the VHL ligand in blue.

PROTAC BTK Degrader-10 (Example 1P) is a PROTAC compound that targets BTK for degradation. It is applicable in the research of chronic lymphocytic leukemia (CLL). [Pink: ligand for target protein; Black: linker; Blue: ligand for E3 ligase Cereblon].

PROTAC BTK Degrader-13 (Compound 25) is a targeted BTK PROTAC degrader with a DC50 of 0.27 μM. It inhibits BTK activity with an IC50 of 0.44 μM and suppresses IL-2-induced T cell kinase (ITK) with an IC50 of 2.16 μM. This compound also inhibits the p38 MAPK signaling pathway, thereby blocking the activation of the BCR (B cell receptor) signaling pathway. [Pink: ligand for target protein BTK ligand 15; Black: linker; Blue: ligand for E3 ligase cereblon]

MT-802 is an effective BTK degrader based on PROTAC technology (DC50: 1 nM). MT-802 has the potential to treat C481S mutant chronic lymphocytic leukemia (CLL).

Lenalidomide-PEG3-iodine, an E3 ligase ligand-linker conjugate, consists of a cereblon-based Lenalidomide ligand and a 3-unit polyethylene glycol (PEG) linker. This compound is utilized in creating various proteolysis targeting chimeras (PROTACs), including the highly effective PROTAC BTK degrader SJF620, which has a degradation concentration 50 (DC50) of 7.9 nM[1].

PROTAC BTK Degrader-2, a potent degrader of BTK through the PROTAC mechanism, effectively diminishes BTK protein levels [1].

PROTAC BTK Degrader-6 (Compound 15), with a DC50 of 3.18 nM, exhibits anti-inflammatory properties by inhibiting NF-κB activation and suppressing the expression of pro-inflammatory cytokines such as IL-1β and IL-6 [1].

PROTAC BTK Degrader-3 is a potent degrader of Bruton's tyrosine kinase (BTK), with a DC50 (median degradation concentration) of 10.9 nM in Mino cells, and shows promise for research into B-cell malignancies, such as chronic lymphoid malignancies [1].

GBD-9, a dual-mechanism degrader, effectively promotes the degradation of BTK and GSPT1 through recruitment of E3 ligase cereblon (CRBN). As a PROTAC molecule, GBD-9 induces BTK degradation, while also acting as a molecular glue for GSPT1 degradation, demonstrating potent inhibition of cancer cell growth [1].

PTD10, a highly potent PROTAC BTK degrader, exhibits a DC50 of 0.5 nM and a KD of 2.28 nM. It effectively degrades BTK in Ramos and JeKo-1 cells with respective DC50 values of 0.5 nM and 0.6 nM. Additionally, PTD10 inhibits cell growth and triggers apoptosis through the activation of both the caspase-dependent and mitochondrial pathways, making it suitable for research on B-cell dysregulation [1].