What should I do if I become resistant to Ritlecitinib?

Ritlecitinib (Ritlecitinib) is the first new covalent kinase inhibitor with significant selectivity for Janus kinase 3 (JAK3). Laboratory experiments have shown that ritexitinib can inhibit the function of signaling molecules and immune cells that cause autoimmune hair loss in patients with alopecia areata (AA).

Ritexitinib is an orally administered, selective JAK3 inhibitor. This selectivity is due to the irreversible covalent binding of ritexitinib to Cys-909 in JAK3. In other JAK isoforms, Cys-909 is replaced by a serine residue. Its half-maximal inhibitory concentration (IC50) for JAK3 inhibition is 33.1nM, but it has no inhibitory activity (IC50>10000nM) against other JAK kinases (JAK1, JAK2 and TYK2), which means that the drug has good selectivity for JAK3 and does not affect JAK1/JAK2 and TYK2 at all. By selectively targeting JAK3, it avoids interleukin (IL)-6 signaling as well as other JAK1-dependent immune regulatory factors.

Ritexitinib is the first JAK3 inhibitor to enter clinical trials and has high selectivity compared with other JAK kinases. After inhibiting BTK, ritexitinib inhibits B cell CD69 surface expression, which is usually expressed after BCR activation with antibodies. Ritexitinibalso inhibitsCD69 surface expression on CD4+ T cells, an effect that is likely driven by ITK inhibition, although a contribution from TEC or RLK inhibition cannot be ruled out. Since ritexitinib is a new drug for the treatment of alopecia areata, it has not yet been marketed in China and has not been included in medical insurance. Its price has not yet been learned. For specific prices and drug details, you can consult a medical consultant.