Mechanism of action

Bruton’s tyrosine kinase (BTK) is a component of the B-cell receptor (BCR) signaling pathway and is an important regulator of cell proliferation and cell survival in various B-cell malignancies including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL) and follicular lymphoma (FL).²

BGB-16673 is an orally available BTK-targeting chimeric degradation activating compound (CDAC) with demonstrated preclinical degradation activity against both wildtype BTK and multiple mutant forms commonly identified in patients who have progressed on BTK inhibitors.¹ BGB-16673 triggers selective BTK degradation via the intracellular ubiquitin-proteasome system. By degrading BTK, BGB-16673 blocks BCR-induced BTK activation and its downstream signaling in a rapid and sustained manner, leading to growth inhibition and cell death in B-cells.

Targeting BTK via an alternative mechanism may overcome the current challenges of BTK inhibitors and may allow continued targeting of a critical pathway in B-cell malignancies.

For a complete list of BGB-16673 clinical trials, view the development program.

BGB-16673 is an investigational compound for which safety and efficacy have not been established. Because of the uncertainty of clinical trials, there is no guarantee that BGB-16673 will receive regulatory approval and become commercially available for the uses being investigated.

References

1. Wang, H., et al. Abstract P1219: BGB-16673, a BTK degrader, overcomes on-target resistance from BTK inhibitors and presents sustainable long-term tumor regression in lymphoma xenograft models. Hemasphere 2023; 7(Suppl): e24358c2.
2. Singh, S. P., Dammeijer, F. & Hendriks, R. W. Role of Bruton’s tyrosine kinase in B cells and malignancies. Mol Cancer 2018; 17(1):57.