01 Jan Abhijit Kulkarni receives AAPS NERDG 2014 Best Podium Presentation in the Academic Research Award (ARA) section
Abhijit Kulkarni is currently a PhD. student in Dr. Ganesh Thakur’s Lab. His research work focuses on the development of novel medications for the treatment of cancer- and chemotherapy- induced inflammation and neuropathic pain as well as curing cognitive impairments in disorders such as Alzheimer’s disease and schizophrenia. He was recently awarded the American Association of Pharmaceutical Scientists – Northeast Regional Discussion Group’s (AAPS NERDG 2014) Best Podium Presentation in the Academic Research Award (ARA) section. This work was around the development of ‘Expeditious Microwave-assisted Synthesis of 4BP-TQS, an ago-PAM of 7 nAChRs, its Stereochemical Requirement and the Target Amino Acids Responsible for Activity’. Despite all the advances in prevention, early detection and newer and more effective treatment modalities, cancer in general remains one of the most debilitating and deadly diseases and is the second leading cause of mortality in the United States. For those who are fighting cancer, the most fearsome symptom regardless of the cancer type is the pain associated with cancer itself and the chemotherapy induced neuropathy leading to persistent and neuropathic pain. The repertoire of approved analgesic drugs like traditional analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids have significant limitations particularly with their long term use as well as the associated side effects. Chemotherapy induced neuropathy limits the dose of anti-cancer drugs and thus reduces their effectiveness. Hence, novel and effective alternatives as cancer and chemotherapy induced chronic neuropathic pain pharmacotherapies are needed. 7 nicotinic acetylcholine receptor (nAChR) orthosteric agonists significantly reduce neuropathic pain clinically and experimentally. However, due to rapid activation and desensitization kinetics of these receptors, their development as clinical candidates has met with limited success. Alpha7 nAChR is also a promising target for improving cognitive impairments in diseases such as Alzheimer’s disease (AD). Desensitization of these receptors by orthosteric agonists has raised concerns regarding their utility as clinical candidates. Alternative strategy is to develop allosteric agonists – positive allosteric modulators (ago-PAMs) that occupy distinct site(s) on the receptor and activate the receptor function, and 4BP-TQS was found to be one such ligand. His goal is to develop a set of novel, selective and potent 7 nAChR ago-PAMs with efficacy in preclinical animal models of acute inflammation and chronic neuropathic pain as well as memory that will be drug candidates for further development of pharmacotherapies.