Biocatalysis and Organic Synthesis Group, Chemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazils

Pirtobrutinib (Jaypirca) is a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor developed by Eli Lilly indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.


BTK plays a crucial role in B cell development as it is required for transmitting signals from the pre-B cell receptor that forms after successful immunoglobulin heavy chain rearrangement. B cells belong to the lymphocyte subtype of white cells and are responsible for producing antibodies. However, uncontrolled growth of some B cells can lead to cancer. BTK is a crucial enzyme in B cell stimulation and survival, and pirtobrutinib inhibits BTK in a distinct manner compared to the prototypical BTK inhibitor, ibrutinib. Unlike ibrutinib, pirtobrutinib binds to BTK differently, preventing the genetic alteration of residue C481 at the active site in BTK. This mutation can make some t ... ...