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Going small to win big: Fragment-based screening in drug discovery

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18 7 Hadjuk PJ, Greer J. A decade of fragment-based drug design: strategic advances and lessons learned. Nature Reviews Drug Discovery. 2007 March; 6:211-219. 8 Koch S, de Wit JG, Vos I, et al. Lipids activate SecA for high affinity binding to the SecYEG complex. J Biol Chem. 2016 Oct 21; 291(43):22534-22543. 9 Kranz JK, Schalk-Hihi C. Protein thermal shi s to identify low molecular weight fragments. Methods Enzymol. 2011; 493:277-98. 10 Lamoree B, Hubbard RE. Using Fragment-Based Approaches to Discover New Antibiotics. SLAS Discov. 2018 Jul; 23(6):495-510. 11 Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov. 2007 Nov; 6(11):881-90 12 Lou J, Finegan TM, Mohsen P, Hatton TA, Laibinis PE (1999) Fluorescence-based thermometry: principles and applications. Rev Anal Chem. 1999; 18(4):235–284. 13 Magnez R, Thiroux B, Taront S, Segaoula Z, Quesnel B, Thuru X. PD-1/PD-L1 binding studies using microscale thermophoresis. Sci Rep. 2017 Dec 15; 7(1):17623. 14 Neumann A, Neumann AL, Bartoschik T, et al. Fast molecular interaction screening of epigenetic gene regulator G9a with fragments from a large chemical space. 2019. Application Note, NanoTemper Technologies, Inc. 15 Niesen FH, Berglund H, Vedadi M. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat Protoc. 2007; 2(9):2212-21. 16 Qu Y, Gharbi N, Yuan X, et al. Axitinib blocks Wnt/beta-catenin signaling and directs asymmetric cell division in cancer. Proc Natl Acad Sci USA. 2016 Aug 16; 113(33):9339-44. 17 Rainard JM, Pandarakalam GC, McElroy SP. Using Microscale Thermophoresis to Characterize Hits from High-Throughput Screening: A European Lead Factory Perspective. SLAS Discov. 2018 Mar; 23(3):225-241. 18 Raymond J-L, van Deursen R, Blum LC and Ruddigkeit L. Chemical Space as a source for new drugs. Med. Chem. Commun., 2010 (1): 30-38.

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