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Your search keyword '"Wittwer, Arthur J."' showing total 3 results
Start Over Author "Wittwer, Arthur J." Publisher american chemical society
3 results on '"Wittwer, Arthur J."'

1. Substrate-dependent inhibition kinetics of an active site-directed inhibitor of ADAMTS-4 (aggrecanase 1)

Author

Wittwer, Arthur J., Hills, Robert L., Keith, Robert H., Munie, Grace E., Arner, Elizabeth C., Anglin, Charles P., Malfait, Anne-Marie, and Tortorella, Micky D.

Subjects
Peptides -- Research, Amino acid sequence -- Research, Protein binding -- Research, Biological sciences, Chemistry
Abstract

Study is conducted to compare the inhibition kinetics of a hydroxamate based inhibitor of ADAMTS-4 using a small peptide substrate versus the native substrate, aggrecan. It also defines the mode of inhibition of the ADAMTS-4 inhibitor with both substrates.

Published
2007

3. Aminopyrazole Carboxamide Bruton's Tyrosine Kinase Inhibitors. Irreversible to Reversible Covalent Reactive Group Tuning.

Author

Schnute ME, Benoit SE, Buchler IP, Caspers N, Grapperhaus ML, Han S, Hotchandani R, Huang N, Hughes RO, Juba BM, Kim KH, Liu E, McCarthy E, Messing D, Miyashiro JS, Mohan S, O'Connell TN, Ohren JF, Parikh MD, Schmidt M, Selness SR, Springer JR, Thanabal V, Trujillo JI, Walker DP, Wan ZK, Withka JM, Wittwer AJ, Wood NL, Xing L, Zapf CW, and Douhan J 3rd

Abstract

Potent covalent inhibitors of Bruton's tyrosine kinase (BTK) based on an aminopyrazole carboxamide scaffold have been identified. Compared to acrylamide-based covalent reactive groups leading to irreversible protein adducts, cyanamide-based reversible-covalent inhibitors provided the highest combined BTK potency and EGFR selectivity. The cyanamide covalent mechanism with BTK was confirmed through enzyme kinetic, NMR, MS, and X-ray crystallographic studies. The lead cyanamide-based inhibitors demonstrated excellent kinome selectivity and rat pharmacokinetic properties., Competing Interests: The authors declare no competing financial interest.

Published
2018
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