enmd-2076 and Hematologic-Neoplasms

Aurora kinases are key regulators of mitosis and inhibition of Aurora kinase activity is a rational therapeutic strategy in the treatment of solid tumors and hematological malignancies.. This paper will provide an updated summary of preclinical and clinical experience with ENMD-2076 in hematological malignancies. The MEDLINE (OVID) (1980 through 31 January 2012) was searched with the term combinations including Aurora, multiple myeloma, leukemia, lymphoma, myelodysplastic syndrome and myeloproliferative neoplasms. In addition, the American Society of Clinical Oncology (ASCO) (1997 - 2011) and the American Society of Hematology (ASH) (1997 - 2011) conference proceedings were searched for reports of new or ongoing trials.. ENMD-2076 is a multi-kinase inhibitor, with activity against Aurora A kinase, FLT3, c-KIT, c-FMS and VEGFR-2 and -3. It appears to be tolerable, exhibits favorable pharmacokinetic profiles and has activity in patients with acute myeloid leukemia and multiple myeloma. Further evaluation with cytotoxic chemotherapy and targeted agents, which affect different pathways and have non-overlapping toxicities, in patients with hematological malignancies are warranted.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Aurora Kinases; Hematologic Neoplasms; Humans; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Pyrazoles; Pyrimidines