Brigatinib
chemical compound
Brigatinib, sold under the brand name Alunbrig among others, is a small-molecule targeted cancer therapy being developed by Ariad Pharmaceuticals, Inc. Brigatinib acts as an inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR), as well as several nonreceptor tyrosine kinases such as FAK, FAK2, and FER. It shows activity against ALK-positive non–small cell lung cancer, ALK-positive anaplastic large cell lymphoma (ALCL), and NF2-related schwannomatosis.
Brigatinib could overcome resistance to osimertinib conferred by the EGFR C797S mutation if it is combined with an anti-EGFR antibody such as cetuximab or panitumumab.
Mechanism of action
Brigatinib acts as an inhibitor of the ALK and mutated EGFR, as well as several nonreceptor tyrosine kinases such as FAK, FAK2, and FER.
ALK was first identified as a chromosomal rearrangement in anaplastic large cell lymphoma (ALCL). Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as ALCL. Since ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy.
Brigatinib inhibits ROS proto-oncogene-1 fusions and EGFR mutations and has a remarkable effect on the central nervous system.
Epidermal growth factor receptor (EGFR) is another validated target in NSCLC. Additionally, the T790M "gatekeeper" mutation is linked in approximately 50 percent of patients who grow resistant to first-generation EGFR inhibitors. While second-generation EGFR inhibitors are in development, clinical efficacy has been limited due to toxicity thought to be associated with inhibiting the native (endogenous or unmutated) EGFR. A therapy designed to target EGFR, the T790M mutation but avoiding inhibition of native EGFR is another promising molecular target for cancer therapy.
History
Regulatory approval
Ariad Pharmaceuticals, Inc. filed an investigational new drug (IND) application to the US FDA on August 29, 2016.
“Brigatinib” enters the record as chemical compound. Crown Archives preserves that source wording while asking what Brigatinib, chemical and compound can confirm, complicate or overturn.
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This entry incorporates text from “Brigatinib” on English Wikipedia. Contributors are listed in the page history. Text is available under the Creative Commons Attribution-ShareAlike 4.0 License. Selected authority identifiers and statements are retrieved from Wikidata under CC0; their references and qualifiers remain part of the verification path.