Dr. Sridhar’s research group focuses on the development new and novel cancer therapeutics using computational modeling tools and organic synthetic techniques. Oncogenic protein kinases are the target biomolecules forthe ATP-competitive small molecule agents developed as potential cancer therapeutics.
Three kinases a retargeted for cancer therapeutics development. Overexpression of Ribosomal protein S6K1 is evidenced in ER+, HER2D16breast cancer. Over expression of S6K1 is a biomarker for aggressive metastatic forms of breast cancer. S6K1 inhibitors can serve as therapeutics for all types of breast cancer. A new series of insoindoline-1,3-diones are under development in the lab as specific S6K1 inhibitors for breast cancer growth inhibition. Depending on the structure features of the isoindoline-1,3-diones the kinase inhibition specificity and potency profiles changes. We have identified molecules that inhibit specific mutants of RET kinase and their effect on growth inhibition of RET mutant evidenced cancers are being explored. WEE1 is the third kinase that is specifically inhibited by certain derivatives ofisoindoline-1,3-diones. These compounds are also under investigation as cancer therapeutics.
Two new series of molecules are being developed as casein kinase 1 d/e inhibitors. CK1d/e are oncogenic, play critical roles in circadian rhythm and are implicated in neurodegenerative disorders characterized by tauopathy. The efficacy of the CK1d/e inhibitors on reducing the hyperphosphorylation of tau protein and regulating the period proteins involved in circadian rhythm is being explored.
Ph.D. from Indian Institute of Chemical Technology, Osmania University, India
ORCID: 0000-0002-4424-9874
Topic: Kinase inhibitors, cancer, tauopathy, circadian rhythm
