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Drug Discovery and Development

Development of novel drug for the prevention of End-stage Renal Disease (ESRD)

Kidney failure or renal failure is a condition wherein the kidneys are unable to perform their basic functions adequately and the metabolic wastes and toxins such as Urea, Creatinine, Uric-acid, Ammonia, Creatine etc. starts accumulating in the serum and are abnormally elevated in our body. Physiologically, renal failure could be seen as a rapid decrease in the Glomerular Filtration Rate (GFR). Chronic kidney diseases may have significant repercussions on the overall health and other diseases such as cardiovascular or neurological disorders.


Chronic Reflux nephropathy (CRN) is a condition wherein the kidneys fail to function adequately due to congenital malformations in the structural morphology of the kidneys and the organs are severely scarred and small, underdeveloped in size. They are usually associated with chronic pyelonephritis, (CPN) are almost always associated with the incidence of vesico-ureteric reflux (VUR). Congenital reflux nephropathy compounded with Vesico-ureteric reflux (VUR) and Posterior Urethral Valves (PUV) is predominantly found in male, and the condition mostly leads to End-stage Renal Disease.


Recent developments in the biological sciences and genomics are mainly pertaining with the human kinome, signal transduction pathways and cell – cell signalling. Thus these advancements have led to the detection of several key pharmaceutical targets that are involved in a wide range of diseases, including cancer. This novel trend of drug discovery based on pathway analysis is known as Systemic Medicine, as it involves system-level targets for drugs. As mentioned above, TGF- and p-38 MAPK are the key modulators for pro-inflammatory and pro-apoptotic signalling, our research is focused on screening of natural compounds for the inhibitory properties for these proteins. Thus the main goal of our research is to predict and characterize effective druggable molecules from naturally occurring plant alkaloids of random nature for inhibitory activity for p-38 MAPK in order to ameliorate progressive renal Failure at an earlier stage, before progressing to End-stage Renal Failure. This would not only provide improvement and diversification of drug usages and characterization, but would also help in the development of COST-EFFECTIVE novel drug for the prevention of End-stage Renal Disease (ESRD) in the future, thereby contribute significantly towards the betterment of the society.


Publications:

1. Avinash Ramani and G. Ramesh Kumar. In-silico assessment of Antagonist Properties for TGF - b Type – II Receptor as a Therapeutic approach for the Prevention of Progressive End Stage Renal Failure. Poster presented at VIIIth Asia-Pacific Bioinformatics Conference - IISc-NCBS, Bangalore (January 18-21).


2. Avinash Ramani and G. Ramesh Kumar. Virtual Screening of Natural Compounds for the Assessment of Antagonist Properties for TGF -b Type – II Receptor Kinase as a Therapeutic approach for the Prevention of Progressive End Stage Renal Failure in children with CAKUT. Oral Presentation at International Symposium on "Gene to Vial" - Concept for Biotechnology based Health Care Molecules - VIT University - Vellore (February 7 -10).


3. Avinash Ramani and G. Ramesh Kumar. Novel Therapeutic Approaches for Prevention of ESRD in children with common forms of CAKUT based on Population genetics and Bioinformatics analysis. Review Paper and Oral Presentation at International Conference in Systemics, Cybernetics and Informatics, Hyderabad (January 27 – 30).


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