Issue link: https://resources.nanotempertech.com/i/1133236
16 Healthy pipeline for fragment- based drug discovery As of September 2016, there were a total of 30 drugs in clinical trials that were produced from fragment-based campaigns; 17 were in phase 1, 10 in phase 2, and 3 in phase 3. Two drugs from fragment-based methods have been approved so far by the FDA and in Europe – Vemurafenib against BRAF- V600E for late-stage melanoma and Venetoclax against BCL-2 for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) 5 . protein kinases can usually be generated in the required amounts for purposes of X-ray structural analysis, there are many more kinds of druggable protein targets beyond kinases for which such amounts of material are not so readily prepared. Over-reliance on traditional methods can thereby form a constraint on the types of targets that can be screened. However, the advantages of fragments have likely only begun to be exploited, as fragments can be found for most targets including those that fail in HTS. For instance, the greater chemical space coverage that fragments afford can provide new chemical entities for even well-characterized targets such as the kinases mentioned above. But the real promise of FBDD is to allow challenging target classes such as protein-protein interactions and GPCRs to be successfully approached. And while the future of FBDD will depend in part on the ability to express difficult proteins in sufficient quantity and quality for biophysical screening and structural studies, screening methods that require only small amounts of target and are amenable to alternative buffer formulations may also hold the key. Sensitive biophysical methods such as TRIC that do not require large quantities of protein and can characterize binding affinities in solution (without the need for immobilization) whether performed in serum, crude cell lysates, or on proteins in liposomes, could greatly expand the target universe for FBDD 22, 13, 23 . Consequently, NMR, SPR, and X-ray crystallography's inherent limitations leave room for other techniques, such as TRIC, to showcase their own advantages and be considered the first choice, particularly for challenging target classes. Affordability of FBDD relative to HTS that enables academia to become involved in compound screening holds perhaps some of the most exciting future possibilities in the field of chemical biology. Creative application of fragment libraries combined with cutting-edge biophysical techniques in basic research could lead to discoveries that significantly advance our understanding of complex biological systems.