(657.15) Small molecule inhibitors of Nek2 kinase using a whole animal Nek2 overexpression model

Poster Board Number: A207

Rafael Musayev (Queens College-CUNY, Queens College-CUNY), Lamia Hauter (Queens College-CUNY), Ashif Bhuiyan (Queens College-CUNY, The Graduate Center-CUNY), Asha Santha (Queens College-CUNY, The Graduate Center-CUNY), Anna Dickson (Queens College-CUNY), Alan Finkelstein (Queens College-CUNY), Tanaji Talele (Saint Johns University), Sanjai Pathak (Queens College-CUNY, The Graduate Center-CUNY)

Nek2 kinase, a prominent member of the Never in Mitosis (NIMA) Related Kinases (Neks), is overexpressed in a wide variety of highly aggressive cancers. These include triple-negative breast, cervical, testicular, ovarian, and prostate cancers. Aberrant Nek2 function as a result of cellular overexpression has been associated with drug resistance and cancer metastasis. Despite this, no clinical agent targeting Nek2 kinase has been developed thus far. Using a Nek2 overexpression model in Drosophila melanogaster, we have shown that the overabundance of Nek2 kinase can dysregulate intracellular signaling to promote highly invasive cellular migratory and proliferation pathways (e.g. activation of Akt/PI3K pathway). Using the same model system, we also identified a novel, non-toxic drug-like quinoline-based pharmacophore. In this work, we report on the development of a library of potential Nek2 inhibitory compounds derived from this pharmacophore. We anticipate that the lead compounds derived from this study will result in the development of highly effective Nek2-targeting anti-cancer agents with reduced toxicity.