MedKoo product information:

   AP26113

Description of AP26113: AP26113 is an orally available inhibitor of receptor tyrosine kinases anaplastic lymphoma kinase (ALK) and the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Dual ALK/EGFR inhibitor AP26113 binds to and inhibits ALK kinase and ALK fusion proteins as well as EGFR and mutant forms. This leads to the inhibition of ALK kinase and EGFR kinase, disrupts their signaling pathways and eventually inhibits tumor cell growth in susceptible tumor cells. In addition, AP26113 appears to overcome mutation-based resistance. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; ALK dysregulation and gene rearrangements are associated with a series of tumors. EGFR is overexpressed in a variety of cancer cell types. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:  ARIAD Pharmaceuticals, Inc.

AP26113 is a small-molecule targeted cancer therapy, developed by ARIAD Pharmaceuticals, Inc. AP26113 has exhibited activity as a potent dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR). This compound targets a unique genetic feature of cancer cells and ARIAD has begun a Phase 1/2 clinical trial of AP26113 based on patients’ molecular diagnoses in September 2011.  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. (source: http://en.wikipedia.org/wiki/AP26113).

Pre-clinical study if AP26113: In 2010, ARIAD announced results of preclinical studies on AP26113 showing potent inhibition of the target protein and of mutant forms that are resistant to the first-generation ALK inhibitor, which currently is in clinical trials in patients with cancer. ARIAD scientists presented these data at the annual meeting of the American Association for Cancer Research (AACR) in Washington, D.C. in April.  In 2011, ARIAD announced preclinical studies showing that AP26113 potently inhibited activated EGFR or its T790M mutant, both in cell culture and in mouse tumor models following once daily oral dosing. Importantly, the effective oral doses in these preclinical models were similar to those previously shown to be effective in resistant ALK models. When tested against the native form of EGFR, AP26113 lacked activity, indicating a favorable selectivity for activated EGFR. These data were presented at the International Association for the Study of Lung Cancer (IASLC) 14th World Conference on Lung Cancer. (source: http://en.wikipedia.org/wiki/AP26113).