This thesis is divided into four projects exploring uncharted chemical space by DNA encoded library (DEL) screening and photoaffinity labeling. The first project highlights the discovery of dual Bcl-XL /Bcl-2 inhibitors discovered from DEL screening using a fragment pairing strategy. The second project focused on the discovery of a small molecule modulator of the mTORC2 pathway by targeting mSin1, discovered from a library designed to bind to Pleckstrin Homology domains. The third project proposed a chemical genetics investigation of Apicomplexan parasites, and the final project developed the premise of a new microenvironment mapping technology via bioluminescence.