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BCR gene fused ABL kinase is the critical driving force for the Philadelphia Chromosome positive (Ph+) Chronic Myeloid Leukemia (CML) and has been extensively explored as a drug target. With a structure-based drug design approach we have discovered a novel inhibitor CHMFL-074, that potently inhibits both the native and a variety of clinically emerged mutants of BCR-ABL kinase. The X-ray crystal...
Cathepsin B is a lysosomal cysteine proteinase whose expression and trafficking are frequently altered in cancer, and plasma membrane and secreted forms are thought to contribute to the invasive and metastatic properties of malignant tumors. We have manipulated the expression of cathepsin B in several tumor cell lines and measured their capacity to invade through a reconstituted extracellular (...
Cathepsin B is a lysosomal cysteine proteinase whose expression and trafficking are frequently altered in cancer, and plasma membrane and secreted forms are thought to contribute to the invasive and metastatic properties of malignant tumors. We have manipulated the expression of cathepsin B in several tumor cell lines and measured their capacity to invade through a reconstituted extracellular (...
The inhibitor CA-074 and its membrane-permeable derivative CA-074Me have been widely employed to study the biological function of cathepsin B. These compounds have been described as selective inactivators of cathepsin B with barely detectable action on other cathepsins. However, in this study it is demonstrated that CA-074 and CA-074Me also inactivate cathepsin L in the presence of the thiol re...
BACKGROUND The lysosomal cysteine proteases of the papain family are some of the best studied proteolytic enzymes. Small-molecule inhibitors and fluorogenic substrate mimics have been used to probe the physiological roles of these proteases. A high degree of homology between family members and overlap in substrate specificity have made elucidating individual protease function, expression and ac...
Send offprint requests to: G. Weigelt email: [email protected] ⋆ Based on observations made with ESO telescopes at Paranal Observatory under programme ID 074.A-9025(A).
We present spectra of three gravitational lens systems taken with the Low Resolution Imaging Spectrograph on the W. M. Keck Telescopes. All of the systems were discovered in the JVAS and CLASS radio surveys, which were designed to find lenses suitable for measuring H0. Previous spectra of these systems had low signal-to-noise ratios, and only one of the source redshifts was secure. Our observat...
We have searched for molecular absorption lines at millimeter wavelengths in eleven gravitational lens systems discovered in the JVAS/CLASS surveys of flat spectrum radio sources. Spectra of only one source 1030+074 were obtained in the 3-, 2and 1.3-millimeter band at the frequencies corresponding to common molecular transitions of CO and HCO as continuum emission was not found in any of the ot...
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