CI-1033 (N-[4-[N-(3-chloro-4-fluorophenyl)amino-7-[3-(4-morpholynyl)propoxy]quinazolin-6-yl]acrylamide, PD 0183805-mesylate salt) was identified as a potent, selective inhibitor of erbB family tyrosine kinases, which are overexpressed in a number of solid tumors and have been shown to be involved in tumor progression. Because objective response of clinical patients to erbB-targeted therapies li...

Recent clinical data indicates that the emergence of mutant drug-resistant kinase alleles may be particularly relevant for targeted kinase inhibitors. In order to explore how different classes of targeted therapies impact upon resistance mutations, we performed EGFR (epidermal-growth-factor receptor) resistance mutation screens with erlotinib, lapatinib and CI-1033. Distinct mutation spectra we...

PURPOSE To determine the tolerability and pharmacokinetics of oral CI-1033, a pan-erbB tyrosine kinase inhibitor, administered over 14 consecutive days of a 21-day cycle. DESIGN Phase 1, multicenter trial involving patients with solid tumors that are refractory to standard therapy. CI-1033 was administered initially at 300 mg/day to a minimum cohort of three patients. Dose escalation proceede...

a Department of Chemistry and Biomolecular Science, and NanoBio Laboratory (NABLAB), Clarkson University, Potsdam NY 13699-5810, USA b Instituto de Catalisis y Petroleoquimica, CSIC. C/ Marie Curie, 2. 28049 Madrid, Spain c Procter and Gamble Company, Mason Business Center, 8700 Mason Montgomery Road Mason, Ohio 45040, USA d Research and Development Department, Procter and Gamble Company, Cinci...

In this study, Four Wave Mixing (FWM) characteristics in photonic crystal fibers are investigated. The effect of channel spacing, phase mismatching, and fiber length on FWM efficiency have been studied. The variation of idler frequency which obtained by this technique with pumping and signal wavelengths has been discussed. The effect of fiber dispersion has been taken into account; we obtain th...