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Your search keyword '"Allen, Vivienne"' showing total 2 results
Start Over Author "Allen, Vivienne" Topic pyrazoles
2 results on '"Allen, Vivienne"'

1. Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma.

Author

Wang X, Blackaby W, Allen V, Chan GKY, Chang JH, Chiang PC, Diène C, Drummond J, Do S, Fan E, Harstad EB, Hodges A, Hu H, Jia W, Kofie W, Kolesnikov A, Lyssikatos JP, Ly J, Matteucci M, Moffat JG, Munugalavadla V, Murray J, Nash D, Noland CL, Del Rosario G, Ross L, Rouse C, Sharpe A, Slaga D, Sun M, Tsui V, Wallweber H, Yu SF, and Ebens AJ

Subjects
Animals, Antineoplastic Agents chemical synthesis, Antineoplastic Agents metabolism, Cell Line, Tumor, Dogs, Female, Humans, Macaca fascicularis, Madin Darby Canine Kidney Cells, Male, Mice, SCID, Molecular Structure, Protein Binding, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors metabolism, Proto-Oncogene Proteins c-pim-1 metabolism, Pyrazoles chemical synthesis, Pyrazoles metabolism, Rats, Sprague-Dawley, Structure-Activity Relationship, Xenograft Model Antitumor Assays, Antineoplastic Agents therapeutic use, Multiple Myeloma drug therapy, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins c-pim-1 antagonists & inhibitors, Pyrazoles therapeutic use
Abstract

Pim kinases have been targets of interest for a number of therapeutic areas. Evidence of durable single-agent efficacy in human clinical trials validated Pim kinase inhibition as a promising therapeutic approach for multiple myeloma patients. Here, we report the compound optimization leading to GDC-0339 (16), a potent, orally bioavailable, and well tolerated pan-Pim kinase inhibitor that proved efficacious in RPMI8226 and MM.1S human multiple myeloma xenograft mouse models and has been evaluated as an early development candidate.

Published
2019
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2. Discovery of a series of imidazopyrazine small molecule inhibitors of the kinase MAPKAPK5, that show activity using in vitro and in vivo models of rheumatoid arthritis.

Author

Andrews MJ, Clase JA, Bar G, Tricarico G, Edwards PJ, Brys R, Chambers M, Schmidt W, MacLeod A, Hirst K, Allen V, Birault V, Le J, Harris J, Self A, Nash K, and Dixon G

Subjects
Animals, Antirheumatic Agents pharmacokinetics, Antirheumatic Agents pharmacology, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid enzymology, Binding Sites, High-Throughput Screening Assays, Humans, Hydrogen Bonding, Imidazoles pharmacokinetics, Imidazoles pharmacology, Intracellular Signaling Peptides and Proteins metabolism, Models, Molecular, Protein Binding, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors pharmacology, Protein Serine-Threonine Kinases metabolism, Pyrazoles pharmacokinetics, Pyrazoles pharmacology, Rats, Small Molecule Libraries, Structure-Activity Relationship, Antirheumatic Agents chemical synthesis, Imidazoles chemical synthesis, Intracellular Signaling Peptides and Proteins antagonists & inhibitors, Protein Kinase Inhibitors chemical synthesis, Protein Serine-Threonine Kinases antagonists & inhibitors, Pyrazoles chemical synthesis
Abstract

MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Published
2012
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