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  • An orally bioavailable, Bcr-Abl tyrosine kinase inhibitor, with potential antineoplastic activity. Designed to overcome resistance of tumor cells to second generation Bcr-Abl inhibitors, PF-114 targets and binds to the Bcr-Abl fusion oncoprotein, including those fusion proteins with the \'gatekeeper\' resistance mutation T315I, an amino acid substitution at position 315 in Bcr-Abl from a threonine (T) to an isoleucine (I). This inhibits Bcr-Abl-mediated proliferation of, and enhances apoptosis in, Philadelphia chromosome-positive (Ph+) hematologic malignancies. The Bcr-Abl fusion protein is an aberrantly activated tyrosine kinase produced by leukemia cells that contain the Philadelphia chromosome. Check for \'https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C130033\' active clinical trials using this agent. (\'http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C130033\' NCI Thesaurus)
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