PROTAC Bcl-xL degrader-2

PROTAC Bcl-xL degrader-2, based on von Hippel-Lindau ligand, is a potent degrader of Bcl-xL (a Bcl-2 family member), demonstrating an IC 50 of 0.6 nM.

Desmorpholinyl Navitoclax-NH-Me (Desmorpholinyl ABT-263-NH-Me) is a Bcl-xL inhibitor, which can be employed alongside a CRBN ligand to synthesize XZ739, a PROTAC BCL-XL degrader [1] [2].

BCL-xLligand 2 is a ligand for BCL-xL. It can be conjugated with an E3 ligase ligand and a linker to form the Bcl-xL-targeting PROTAC degrader PZ671.

PROTACBcl-xL degrader-4 (Compound 2-38-III) is a Bcl-xL PROTAC degrader with significant antitumor activity against HepG2 and HUVEC cells. It induces apoptosis by reducing mitochondrial membrane potential and activating the MAPK signaling pathway. PROTACBcl-xL degrader-4 markedly inhibits tumor growth in xenograft mouse models.

XZ739 is a Cereblon-dependent PROTAC BCL-XL degrader, targeting a member of the Bcl-2 family, with a DC50 value of 2.5 nM in MOLT-4 cells after 16 hours of treatment. Additionally, XZ739 elicits cell death via caspase-mediated apoptosis.

PZ703b is a novel BCL-XL PROTAC degrader with enhanced BCL-2 inhibition.

PZ703b hydrochloride, a Bcl-xl PROTAC degrader, effectively induces apoptosis and curbs the proliferation of cancer cells. It is primarily utilized in the study of bladder cancer [1] [2].

PROTAC Bcl-xL degrader-1 is a potent PROTAC composed of a Bcl-xL (Bcl-2 family member) ligand-binding group, a linker, and an IAP E3 ligases binding group, demonstrating effectiveness as a Bcl-xL degrader. It exhibits toxicity towards human platelets and MyLa 1929 cells, with IC50 values of 62 nM and 8.5 μM, respectively [1].

WH244 is a second-generation dual degrader (PROTAC) targeting BCL-2 and BCL-xL proteins. It effectively degrades these proteins with high specificity, exhibiting a DC50 of 0.6 nM for BCL-xL and 7.4 nM for BCL-2. By promoting ubiquitination and subsequent proteasomal degradation of these proteins, WH244 restores apoptotic pathways in cells. The compound shows strong antitumor activity.