XZ739

XZ739, a CRBN-dependent PROTAC BCL-XL degrader with a DC50 value of 2.5 nM in MOLT-4 cells after 16 h treatment. XZ739 also induces cell death through caspase-mediated apoptosis[1].

Signaling Pathways >> Apoptosis >> Bcl-2 Family

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> PROTAC >> PROTAC

Bcl-xL:2.5 nM (DC50)

Cereblon

XZ739 (0.001-10 μM; 48 hours) potently reduces the viability of T-ALL MOLT-4, B-ALL RS4; 11, SCLC NCI-H146 cells, and platelets after 48 h treatment with IC50s of 10.1, 41.8, 25.3, and 1217 nM, respectively. XZ739 has >100-fold selectivity for MOLT-4 cells over human platelets[1]. XZ739 (1.2-300 nM; 16 hours) induces BCL-XL degradation in MOLT-4 cells[1]. The BCL-XL degradation induced by XZ739 in MOLT-4 is rapid, starting within 2 h; and 8 h after XZ739 treatment, more than 96% of the BCL-XL is degraded with 100 nM of XZ739[1]. Cell Viability Assay[1] Cell Line: Human platelets and MOLT-4 cells Concentration: 0.001, 0.01, 0.1, 1, and 10 μM Incubation Time: 48 hours Result: IC50 values were 10.1 nM and 1217 nM for MOLT-4 cells and platelets, respectively. Western Blot Analysis[1] Cell Line: MOLT-4 cells Concentration: 1.2, 3.7, 11, 33, 100, 300 nM Incubation Time: 16 hours Result: Dose-dependently induced BCL-XL degradation.

[1]. Xuan Zhang,et al. Discovery of PROTAC BCL-X L Degraders as Potent Anticancer Agents With Low On-Target Platelet Toxicity. Eur J Med Chem. 2020 Apr 15;192:112186.