What is the mechanism of action of entrectinib? How does it work?

Entrectinib is a tropomyosin receptor tyrosine kinase (TRK)TRKA, TRKB , TRKC, proto-oncogene tyrosine protein kinase ROS1, and anaplastic lymphoma kinase (ALK) inhibitors. Entrectinib was approved by the FDA in August 2019 for the treatment of ROS1-positive metastatic non-small cell lung cancer and NTRK gene fusion-positive solid tumors.

Entrectinib is a tyrosine kinase inhibitor that acts on several receptors. Inhibits tropomyosin receptor tyrosine kinase (TRK) asATPcompetitorTRKA, TRKB , TRKC, and the proto-oncogenes tyrosine-protein kinase ROS1 and anaplastic lymphoma kinase (ALK). 4,5,7TRKReceptors produce cell proliferation through downstream signaling of mitogen-activated protein kinase, phosphoinositide 3-kinase, and phospholipase C-γ. ALKproduces a similar signal by adding downstream JAK/STAT activation. Inhibition of these pathways inhibits cancer cell proliferation and shifts the balance in favor of apoptosis, resulting in tumor size reduction.

The binding rate of entrectinib to plasma proteins exceeds 99%. CYP3A4is responsible for 76% of the entrectinib metabolism in the human body, including the metabolism of the active metabolite M5. M5has pharmacological activity similar to entrectinib, and the steady-state concentration of its parent drug is approximately 40%. In rats, six in vivo metabolites have been identified, includingN-dealkylation, N-oxide, hydroxylation, and glucuronide conjugation metabolites. The half-life of entrectinib is 20 hours. 7The active metabolite M5 has a half-life of 40 hours. The apparent clearance of entrectinib was 19.6L/ hours, while the apparent clearance of the active metabolite M5 was 52.4L/ hours. There are generic drugs in Laos, officially marketed versions, with government approval, retail price of pharmaceuticals in Laos and ASEAN200mg90tablets200 00yuan, 100mg30 tablets6500yuan. If you want to get more high-quality information, you can contact YaDE. YaDE will do its best to learn more about high-quality overseas drugs for you.

xa0