Reference

Novel treatment strategies for chronic myeloid leukemia

All Rights Reserved. Novel treatment strategies for chronic myeloid leukemia. Fausel, Christopher A. (Hematology/Oncology/Bone Marrow Transplant, Indiana University Cancer Center, Indianapolis, IN 46202, USA). American Journal of Health-System Pharmacy, 63(23, Suppl. 8), S15-S20 (English) 2006 American Society of Health-System Pharmacists. CODEN: AHSPEK. ISSN: 1079-2082. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. Purpose: Despite dramatic advances in the treatment of chronic myeloid leukemia (CML), resistance to therapeutic agents has emerged as a significant treatment dilemma. Mutations of the BCR-ABL kinase domain, a common mechanism of resistance to imatinib in CML, are discussed. Summary: Several new targeted kinase inhibitors have reached clin. trials and have proved to be efficacious in halting the oncogenic activity of most BCR-ABL mutants. Dasatinib is 300 times more potent than imatinib at BCR-ABL inhibition, has few side effects, and inhibits the SRC family kinases.Several substances with their cas registry numbers 641571-10-0 and 152459-95-5 may be metioned in this study. Nilotinib inhibits BCR-ABL at 20-50 times more potency than imatinib. Both agents were highly effective in treating chronic phase CML but were less effective at treating accelerated phase CML in early phase clin. trials. In addn. to these specific kinase inhibitors, farnesyl transferase inhibitors are actively being investigated. Vaccination strategies are undergoing clin. investigation transitioning from animal models to human clin. trials. Conclusion: The new kinase inhibitors, dasatinib and nilotinib, are emerging as plausible therapeutic options for the treatment of imatinib-refractory CML. .

Simultaneous determination of AMN107 and Imatinib (Gleevec, Glivec, STI571) in cultured tumour cells using an isocratic high-performance liquid chromatography procedure with UV detection

All Rights Reserved. Simultaneous determination of AMN107 and Imatinib (Gleevec, Glivec, STI571) in cultured tumour cells using an isocratic high-performance liquid chromatography procedure with UV detection. Guetens, Gunther; Prenen, Hans; De Boeck, Gert; van Oosterom, Allan; Schoeffski, Patrick; Highley, Martin; de Bruijn, Ernst A. (Lab of Experimental Oncology, Department of General Medical Oncology, KU Leuven/UZ Gasthuisberg, Louvain, Belg.). Journal of Chromatography, B: Analytical Technologies in the Biomedical and Life Sciences, 846(1-2), 341-345 (English) 2007 Elsevier B.V. CODEN: JCBAAI. ISSN: 1570-0232. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A reversed phase high-performance liq. chromatog. (HPLC) method with UV detection was developed for the simultaneous detn. of imatinib (Gleevec, Glivec, STI571) and AMN107 in cultured tumor cells, using clozapine as an internal std. The compds. of interest were extd. by liq.-liq. extn. using TOXI-TUBES A extn. tubes. Chromatog. 220127-57-1 and 641571-10-0 are cas registry numbers of chemicals which are used as reagents here. sepn. was performed on a Phenomenex Gemini C18 reversed phase column (150 mm ′ 2.0 mm, 5 mm particle size), using a mixt. of 65% CH3OH (methanol) and 35% NH4Ac (Ammonium acetate) buffer (20 mM, pH 10). Sepn. was achieved under isocratic conditions at a flow rate of 0.5 mL/min. Imatinib, clozapine and AMN107 are detected by UV detection at 260 nm. Calibration curves were linear from 50 to 7500 ng/mL with correlation coeffs. (r 2) better than 0.998. The limit of quantitation (LOD) was 50 ng/mL. The method has been successfully applied to a cellular kinetics study. .