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Perera TPS, et al., “Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor.” Mol Cancer Ther, 2017, Vol 16, No. 6 pp. 1010– 1020. DOI: 10.1158/1535-7163.MCT-16-0589

Perera TPS, et al., “Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor.” Mol Cancer Ther, 2017, Vol 16, No. 6 pp. 1010– 1020. DOI: 10.1158/1535-7163.MCT-16-0589

Johnson et al., “A Fragment-Derived Clinical Candidate for Antagonism of X-Linked and Cellular Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1H,2H,3H-pyrrolo[3,2-b]pyridin-1-yl)-2-[(2R,5R)-5-methyl-2-([(3R)-3-methylmorpholin-4-yl]methyl)piperazin-1-yl]ethan-1-one (ASTX660).” J. Med. Chem., 2018, DOI: 10.1021/acs.jmedchem.8b00900

Abstract Inhibitor of apoptosis proteins (IAPs) are promising anticancer targets, given their roles in the evasion of apoptosis. Several peptidomimetic IAP antagonists, with inherent selectivity for cellular IAP (cIAP) over X-linked IAP (XIAP), have been tested in the clinic. A fragment screening approach followed by structure-based optimization has previously been reported that resulted in a […]

Sipthorp et al., ” Visualization of Endogenous ERK1/2 in Cells with a Bioorthogonal Covalent Probe.” Bioconjugate Chemistry, (JUN 2017) Vol. 28, No. 6, pp. 1677-1683; DOI: 10.1021/acs.bioconjchem.7b0015

Abstract The RAS–RAF–MEK–ERK pathway has been intensively studied in oncology, with RAS known to be mutated in ∼30% of all human cancers. The recent emergence of ERK1/2 inhibitors and their ongoing clinical investigation demands a better understanding of ERK1/2 behavior following small-molecule inhibition. Although fluorescent fusion proteins and fluorescent antibodies are well-established methods of visualizing […]

Lebraud et al., “Protein degradation: a validated therapeutic strategy with exciting prospects.” Essays in Biochemistry (2017) 61 517–527; DOI: 10.1042/EBC20170030

Abstract In a time of unprecedented challenges in developing potent, selective and well-tolerated protein inhibitors as therapeutics, drug hunters are increasingly seeking alternative modalities to modulate pharmacological targets. Selective inhibitors are achievable for only a fraction of the proteome, and are not guaranteed to elicit the desired response in patients, especially when pursuing targets identified […]

Price et al., “Fragment-based drug discovery and its application to challenging drug targets.” Essays in Biochemistry (2017) 61 475–484; DOI: 10.1042/EBC20170029

Abstract Fragment-based drug discovery (FBDD) is a technique for identifying low molecular weight chemical starting points for drug discovery. Since its inception 20 years ago, FBDD has grown in popularity to the point where it is now an established technique in industry and academia. The approach involves the biophysical screening of proteins against collections of […]