MS-553 + acalabrutinib

MS-553 + acalabrutinib is a combination therapy being investigated primarily for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)[1][3][7]. MS-553 is a small molecule inhibitor targeting protein kinase C beta (PKCβ), which is a key signaling molecule downstream of Bruton tyrosine kinase (BTK) in the B cell receptor (BCR) pathway. MS-553 is being evaluated in clinical studies for its potential to inhibit BCR signaling and provide therapeutic benefit, especially for patients with CLL who are refractory or resistant to covalent BTK inhibitors such as ibrutinib or acalabrutinib[3][5]. Acalabrutinib is a covalent, second-generation BTK inhibitor approved for CLL, SLL, and mantle cell lymphoma (MCL), working by irreversible inhibition of BTK enzymatic activity, thus blocking key signaling pathways required for malignant B-cell proliferation and survival[2][6]. The rationale for the combination is mechanistic: PKCβ inhibition by MS-553 may block signaling downstream of BTK and synergize with BTK inhibition by acalabrutinib, potentially overcoming resistance to BTK inhibitors and providing more effective control of the disease[1][3][5][7]. Early clinical data show that MS-553 is well tolerated, with most toxicities being gastrointestinal and not overlapping with those of BTK inhibitors[1]. The combination is currently under investigation in Phase 1/2 trials in high-risk and refractory CLL patient populations[7].

Other names

MS-553 + acalabrutinib