Preclinical disposition and pharmacokinetics-pharmacodynamic modeling of biomarker response and tumour growth inhibition in xenograft mouse models of G-573, a MEK inhibitor.
AuthorsChoo EF, Belvin M, Chan J, Hoeflich K, Orr C, Robarge K, Yang X, Zak M, Boggs J,
JournalXenobiotica
PubMed ID20836753
The mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) pathway is a key signalling pathway that regulates cell proliferation. G-573 is an allosteric inhibitor of MEK that is both potent and selective. The objectives of these studies were to characterize the disposition of G-573 in preclinical species and to determine the relationship ... More
Input-output behavior of ErbB signaling pathways as revealed by a mass action model trained against dynamic data.
AuthorsChen WW, Schoeberl B, Jasper PJ, Niepel M, Nielsen UB, Lauffenburger DA, Sorger PK,
JournalMol Syst Biol
PubMed ID19156131
The ErbB signaling pathways, which regulate diverse physiological responses such as cell survival, proliferation and motility, have been subjected to extensive molecular analysis. Nonetheless, it remains poorly understood how different ligands induce different responses and how this is affected by oncogenic mutations. To quantify signal flow through ErbB-activated pathways we ... More