Other likely targets of 1-NA-PP1 have been demonstrated and may account for this effect. In summary, we have identified a new, highly selective, and cellpermeable PKD small molecule inhibitor, 1-NA-PP1. This compact pyrazolopyrimidine possesses potent antitumor activities in prostate cancer cells, thus suggesting its further development as a potential drug candidate. Additionally, this compound may be valuable for use in a chemical genetic approach with the analogsensitive PKD to investigate PKD-specific functions and signaling mechanisms in diverse biological systems. The number of cancer survivors in the United States has risen to an estimated 12 million in 2012 resulting in a heightened awareness of long-term toxicities and the impact of treatment on quality of life. CIPN is one of the most common and potentially permanent side effects for many anti-cancer agents and its incidence has been reported to be as high as 20�C40% among all cancer LY2109761 patients undergoing chemotherapy. General symptoms start in the fingers and toes and spread progressively up the extremities as CIPN worsens and include numbness, tingling, burning, loss of tendon reflexes and vibration sensation, and spontaneous or evoked pain. There is substantial inter-patient and drug-dependent variability in time to symptom onset, time to peak symptoms, severity of peak symptoms, and reversibility. Management is complicated by the lack of reliable means to identify at-risk patients. If patients at high risk could be identified, alternative chemotherapy regimens with similar efficacy could be considered. In efforts to identify genetic variants associated with chemotherapeutic toxicities including CIPN, researchers have performed genome-wide association studies in clinical trials. The challenges of clinical GWAS, including accurately phenotyping large patient cohorts receiving the same drug regimen and obtaining replication cohorts, have led to the development of cell based models as a complementary method to identify variants and functionally validate findings resulting from the clinical studies. The extensively genotyped International HapMap lymphoblastoid cell line model has been useful for this purpose and significant overlap between genetic variants associated with cellular sensitivity to paclitaxel and paclitaxel-induced clinical neuropathy has been demonstrated. Follow up studies have utilized either LCLs or Neuroscreen-1 cells to functionally validate the R428 involvement of GWAS findings in response to chemotherapeutics. Neither cellular model represents genetically diverse human peripheral neurons, the tissue of CIPN toxicity.