Screening libraries of molecules, e.g., to identify drugs and targeting molecules for carrying drugs, by administering a radiolabeled library to animals, and analyzing the distribution of radioactivity

摘要

Screening (M1) a library of molecules (I) comprising administration of radiolabeled (I) to animals, sacrificing at least one animal, analyzing the distribution of radioactivity in the animal tissue, isolating radioactive fractions, and characterizing (I) in the fractions, is new. Screening (M1) a library of molecules (I) comprises: (a) administration of radiolabeled (I) to animals; (b) sacrificing at least one of the animals; (c) analyzing the distribution of radioactivity in the animal tissue by imaging tissue sections or isolated organs; (d) selecting sections or organs in which radioactivity is detected and isolating the radioactive fractions (e.g. by solvent extraction or chromatography); and (e) characterizing (I) in the radioactive fractions (e.g. by chromatography or mass spectrometry). Independent claims are also included for: (1) a variant of M1, in which step (b) is replaced by analyzing the tissue distribution of (I) by imaging in vitro using an isolated biological sample selected from cells, tissue slices and organs, followed by selection etc. as above; (2) analogous methods of identifying and studying target molecules (II) selectively expressed in organs or tissues, involving steps (a) - (e) as above (either variant), then contacting (I) with extracted organ, tissue or cells under suitable conditions to form a (I)/(II) complex and isolating (II) from the complex; (3) kits for carrying out the processes, including at least one library of radiolabeled compounds (I) and detection and analysis systems for radioactive products; (4) a new product obtained by the screening processes, consisting of a peptide of formula (Ia), optionally in radiolabeled form. propyl-NH-Arg-Phe(PO2-CH2)Leu-Ala-NH2 (Ia).