News analysis of the mechanism of action of serputinib/serpatinib

Selpercatinib/Selpercatinib is a kinase inhibitor. Seputinib inhibits wild-type RET and multiple mutated RET isoforms as well as VEGFR1 and VEGFR3 with IC50 values u200bu200branging from 0.92nM to 67.8nM. In other enzyme assays, seputinib also inhibited FGFR 1, 2, and 3 at higher concentrations that are still clinically achievable. In cell assays, seputinib inhibited RET at concentrations approximately 60-fold lower than FGFR1 and 2 and approximately 8-fold lower than VEGFR3.

Certain point mutations in RET or chromosomal rearrangements involving in-frame fusion of RET with various partners can lead to constitutively active chimeric RET fusion proteins that can act as oncogenic drivers by promoting cell proliferation in tumor cell lines. In in vitro and in vivo tumor models, seputinib showed antitumor activity in cells harboring constitutively activated RET proteins caused by gene fusions and mutations, including CCDC6-RET, KIF5B-RET, RET V804M, and RET M918T. In addition, septinib showed antitumor activity in mice with intracerebral implantation of patient-derived RET fusion-positive tumors.

Up to now, the original research drug is sold in China under the name of Seputinib, but it is not included in medical insurance. The price of each box of 80mg*56 tablets may be more than 10,000 yuan. There are European and American versions of the original drugs sold overseas, with the price of each box ranging from 20,000 to more than 100,000 yuan (prices may fluctuate due to exchange rates). Generic drugs of Seputinib have also been put on the market for sale overseas, and their pharmaceutical ingredients are basically the same as those of the original drugs sold domestically and abroad. For example, the price of 40mg*120 capsules produced by a Laos pharmaceutical factory is more than RMB 4,000 per box (the price may fluctuate due to exchange rates).