ALK Inhibitor X-396
X-396 has been validated in potency and selectivity assays indicating that it is more selective and up to 10 times more potent than competitive ALK inhibitors. X-396 has been active in animal models of non-small cell lung cancer (NSCLC) and neuroblastoma. Importantly, X-396 has shown activity in ALK mutations that confer resistance to other small molecule ALK inhibitors.
Anaplastic lymphoma kinase (ALK) was first identified as a chromosomal rearrangement in anaplastic large cell lymphoma (ALCL). Genetic studies now indicate that in addition to ALCL, abnormal expression of ALK is a key driver of certain types of NSCLC and neuroblastomas, a childhood cancer. Since ALK is generally not expressed in normal adult tissues, it represents a highly promising target for molecularly targeted cancer therapy.
ALK is deregulated by multiple mechanisms including translocation to form a constitutively active fusion protein, activating mutations in the kinase and gene amplification. The EML4-ALK fusion protein is found in a subpopulation of non-smokers that develop NSCLC. Multiple fusion proteins other than EML4-ALK have been identified in patients with ALCL. Similarly, multiple activating mutations in the kinase domain have been found in children with neuroblastoma.
Learn more about the eXalt2 and eXalt3 studies.