Which generation of targeted drugs does Serputinib/Serpatinib (Ruitu) belong to?

Selpercatinib is an oral small molecule targeted drug developed specifically for RET (rearranged susceptibility transcription factor)-driven tumors. Abnormal fusions or point mutations of the RET gene play a key driving role in a variety of solid tumors, especially in non-small cell lung cancer (NSCLC), papillary thyroid carcinoma, and other RET-positive solid tumors.

Abnormal activation of RET kinase will continuously trigger downstream signaling pathways, including RAS-MAPK, PI3K-AKT and JAK-STAT, thereby promoting tumor cell proliferation, survival and metastasis. By selectively inhibiting RET kinase activity, Seputinib can directly block these key signaling pathways, thereby slowing tumor progression and improving the quality of life of advanced patients to a certain extent. In the development process of targeted drugs, seputinib and pralsetinib (BLU-667) are classified as the first generation of specific RET receptor tyrosine kinase (RTK) inhibitors.

Compared with early multi-target RET inhibitors, they are highly selective and only act on RET fusion or mutant kinases, with less inhibition of non-target tyrosine kinases, so side effects are relatively controllable. The emergence of the first generation of RET-specific inhibitors has filled the gap in tumor treatment, allowing patients with RET-positive tumors to receive truly targeted therapy without relying on traditional multi-target inhibitors or chemotherapy regimens.

The advantage of seputinib is not only its selectivity, but also its efficacy against brain metastases. Many patients with advanced RET-positive non-small cell lung cancer are at risk of brain metastasis, and the first-generation RET inhibitors have excellent performance in penetrating the blood-brain barrier and can effectively control brain lesions, which has significant value in clinical application. In addition, seputinib also shows potential in overcoming drug-resistant mutations, providing new treatment opportunities for some patients who have progressed after multi-target inhibitor treatment.

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