Fragment-based drug discovery (FBDD) is a central area of focus for the Young group. Our efforts are aimed at putting an upfront investment into the synthetic chemistry leading to an optimal fragment library to be screened against a variety of challenging disease targets (i.e. K-ras, NF-κB, PTP1B). Prior to our efforts, the use of low molecular weight fragments in FBDD was generally limited to highly planar sp2-carbon containing heterocycles. Based on the principles of diversity-oriented synthesis (DOS), we are preparing a novel sp3-enriched collection of fragments to be screened in a fragment-based paradigm. In addition to accessing a larger chemical space to engage diverse disease targets, the modular and efficient method of synthesis of DOS-based fragments can rapidly provide structure-activity relationships (SAR).