Brigatinib (Brigatinib) belongs to which generation of targeted drugs and its pharmacological characteristics

Brigatinib (Brigatinib, transliterated as brigatinib in some areas) is a second-generation ALK (anaplastic lymphoma kinase) targeted inhibitor. It is mainly used to treat patients with ALK-positive non-small cell lung cancer (NSCLC), especially those who are resistant or intolerant to the first-generation ALK inhibitor crizotinib (Crizotinib). The second generation of targeted drugs has been optimized in terms of structure and selectivity. Compared with the first generation of drugs, it has stronger target affinity, wider coverage of drug-resistant mutations, and better central nervous system penetration.

The main pharmacological mechanism of brigatinib is to inhibit cancer cell proliferation by highly selectively inhibiting the tumor cell growth signaling pathway mediated by the ALK fusion protein. It also has the potential to inhibit ROS1 and EGFR mutations (including some rare EGFR mutations such as T790M). In in vitro and in vivo experiments, brigatinib is active against multiple drug-resistant mutations in ALK (such as G1202R, F1174C, etc.) and is currently one of the second-generation ALK inhibitors covering a wide range of mutations.

Compared with the first-generation crizotinib, brigatinib shows higher progression-free survival and intracranial efficacy. In the pivotal phase III ALTA-1L study, the median progression-free survival of brigatinib in the first-line treatment of ALK-positive lung cancer reached about 24 months, far exceeding that of crizotinib. At the same time, its ability to control brain metastases has also been significantly enhanced, making it one of the more recommended first-line drugs in clinical practice. These advantages are due to its optimized molecular structure, which makes it easier to cross the blood-brain barrier and exert central anti-tumor effects.

Brigatinib has been approved by the drug regulatory authorities of many countries for the treatment of ALK-positive NSCLC patients, including later-line treatment after failure of crizotinib treatment and initial first-line treatment in some countries. It has also been officially launched in China and has been included in medical insurance coverage. WithALKThe mechanism of target resistance is continuously studied in depth, and brigatinib, as an important drug that transitions between the second and third generation ALK-TKIs, is still playing an active role in multiple combination drug and sequential treatment studies. In the future, its scope of use is expected to be further expanded, especially in multi-target synergy and brain metastasis control strategies.

Reference materials:https://www.drugs.com