865704-46-7Relevant articles and documents
CYCLIC PENTAMER COMPOUNDS AS PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) INHIBITORS FOR THE TREATMENT OF METABOLIC DISORDER
-
Page/Page column 318-319, (2020/06/19)
The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I):, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein X1, R1, R2, R3, R4, R5, R6, R6', R7, R7', R8, R9, R9', R10, R11, R12, and n are described herein.
Conjugates of modified cryptophycins and RGD-peptides enter target cells by endocytosis
Nahrwold, Markus,Wei?, Christine,Bogner, Tobias,Mertink, Felix,Conradi, Jens,Sammet, Benedikt,Palmisano, Ralf,Royo Gracia, Soledad,Preu?e, Thomas,Sewald, Norbert
, p. 1853 - 1864 (2013/05/09)
Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized β2-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.