Serputinib/serpatinib belongs to the first generation of targeted drugs

Selpercatinib is a targeted therapy drug classified as a "highly selective RET inhibitor". In the development process of targeted drugs, it is generally considered to be one of the "first exclusive inhibitors" for RET targets, representing the evolutionary direction of targeted drugs from early multi-target inhibitors to highly selective single-target inhibitors. Although the concept of targeted drug generation is mainly applied to drug sequences of mature targets such as EGFR and ALK, from the perspective of drug design concept, septetinib is a "new generation" of precision targeted drugs optimized for known drug resistance and safety issues.

In the history of the treatment of RET-driven non-small cell lung cancer (NSCLC) and thyroid cancer, there was no specific treatment for RET, patients are mostly treated with multi-target tyrosine kinase inhibitors (such as cabozantinib, vandetanib, etc.). Although these drugs can partially inhibit the RET pathway, they often cause a higher proportion of adverse reactions and have limited efficacy because they also inhibit other targets such as VEGFR. The emergence of Seputinib is based on the in-depth analysis of the structure of RET and the realization of high affinity and high selectivity binding to RET kinase through molecular design, which can effectively overcome the shortcomings of early treatment options.

From the perspective of development time and technical level, seputinib can be regarded as the "first-generation exclusive inhibitor" of RET-targeted drugs, but its design concept and clinical performance are similar to third-generation drugs for other targets in terms of accuracy and drug-resistant mutation coverage. It is not only effective in RET fusion-positive patients, but also shows significant efficacy in patients with specific RET point mutations, and it also has certain penetration in patients with CNS (central nervous system) metastasis, which is of great significance for the treatment of advanced lung cancer and thyroid cancer.

Reference:https://en.wikipedia.org/wiki/Selpercatinib