While there are more than 500 kinases encoded within the human genome with over 70 FDA approved small molecule kinase inhibitors, mostly for cancer indications, resistance to first line inhibitors often leads to cancer recurrence and poor prognosis. The development of new drugs that overcome such cancer resistance is still a critical unmet medical need.
Targeting Nuclear Receptors
Nuclear receptors can bind ligand, leading to a conformational change, homo- or hetero-dimerization, nuclear translocation and DNA binding.
Driving Apoptosis of Senolytic Cells
DNA damage, oxidative stress or oncogenic mutations can activate nuclear translocation of p53 and p53 interacting proteins (p53IP), helping to tether p53 onto the transcriptional promoter of pro-senescence protein, p21.