Our group’
s primary interests are:
To discover new chemical entities for the treatment of advanced treatment-refractory cancers and non-oncology indications.
To use chemical and molecular biological approaches to unravel the structure and function of proteins and their underlying mechanism of action.
Our laboratory, in collaboration with Dr. Duane Miller (medicinal chemist), has developed a program to degrade and inhibit androgen receptor (AR) and AR splice variants (AR-SV) by binding to the N-terminus domain of the AR for the treatment of advanced prostate cancer. The program had been outlicensed to Oncternal therapeutics (Oncternal.com). The lead molecule is in phase I clinical trial for the treatment of castration-resistant prostate cancer. We have also created next-generation molecules that irreversibly and covalently bind to AR N-terminus domain and inhibit it. These novel molecules also serve as chemical probes to resolve structure and function of AR and aid in the development of next-generation drugs.
We have also created next-generation molecules that irreversibly and covalently bind to AR N-terminus domain and inhibit it.
The second project utilizes whole genome molecular and epigenetic techniques and chemical biology approaches to elucidate the mechanism of action of various therapeutic targets in breast cancer. We demonstrated that a protein, depending on the context of the disease and the intracellular milieu of cofactors and pioneer transcription factors, can act as an oncogene or a tumor-suppressor. These findings are currently being extended to other cancers and targets.
AR is polymorphed in Kennedy’s disease (Spinal Bulbar Muscular Atrophy (SBMA)), making it the therapeutic target for the disease. The poly-glutamine repeats in the N-terminus domain is expanded in Kennedy’s disease, causing the AR to misfold and form aggregates at neuromuscular junctions. We are developing next-generation AR-targeting drugs to treat this disease, and use these novel molecules to study the mechanisms underlying the disease.
The next drug discovery project targets a kinase for the treatment of ovarian cancer. The molecules have unique mechanism of action. The project is in optimization stage and will be ready for further development once lead molecule is identified.
Ramesh Narayanan Biosketch
Dr. Ramesh Narayanan is a Professor and the Muirhead Chair of excellence in the College of Medicine at the University of Tennessee Health Science Center (UTHSC), Memphis, TN. Dr. Narayanan also serves as the Deputy Director of UTHSC Center for Cancer Research and as the interim Assistant Dean of Research in the College of Medicine. Dr. Narayanan received his Ph.D. in biochemistry at the University of Madras and performed his post-doctoral research in hormone- dependent cancers at Baylor College of Medicine in Houston, TX. After his post-doctoral fellowship, he spent 9 years discovering drugs for oncology and musculoskeletal indications in biotech industry. He last served as the Director of Drug Discovery. In 2014, Dr. Narayanan started his academic pursuit of drug discovery at UTHSC. Dr. Narayanan has published over 70 peer reviewed journal articles (including PNAS, Cell Reports, J Clin Oncol, Nat. Comm., Cancer Research, and others), 6 book chapters, and is a co-inventor in over 125 patents. Dr. Narayanan has an MBA in global business from the University of Memphis. He serves as scientific advisor to Oncternal therapeutics and 1cbio.
Collaborators
Dr. Duane D. Miller – Professor Emeritus, College of Pharmacy, UTHSC
Dr. Man-Ho Choi, Korea Institute of Technology
Dr. Dong-Jin Hwang – Chemist
Dr. Seetharaman Jayaraman, Associate Professor, Pharmacology, UTHSC
Dr. Emmanuel Petricoin Korean Institute of Technology
