Kinesin spindle protein inhibitors as novel payload class for ADCs

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چکیده

منابع مشابه

Optimization of diaryl amine derivatives as kinesin spindle protein inhibitors.

Structure-activity relationship studies of diaryl amine-type KSP inhibitors were carried out. Diaryl amine derivatives with a pyridine ring or urea group were less active when compared with the parent carboline and carbazole derivatives. Optimization studies of a lactam-fused diphenylamine-type KSP inhibitor revealed that the aniline NH group and 3-CF3 phenyl group were indispensable for potent...

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Triphenylbutanamines: Kinesin Spindle Protein Inhibitors with in Vivo Antitumor Activity†

The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-l-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most...

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Downregulation of Kinesin Spindle Protein Inhibits Proliferation, Induces Apoptosis and Increases Chemosensitivity in Hepatocellular Carcinoma Cells

Background: Kinesin spindle protein (KSP) plays a critical role in mitosis. Inhibition of KSP function leads to cell cycle arrest at mitosis and ultimately to cell death. The aim of this study was to suppress KSP expression by specific small-interfering RNA (siRNA) in Hep3B cells and evaluate its anti-tumor activity. Methods: Three siRNA targeting KSP (KSP-siRNA #1-3) and one mismatched-siRNA (...

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Targeting the kinesin spindle protein: basic principles and clinical implications.

Kinesin spindle protein (KSP), a member of the kinesin superfamily of microtubule-based motors, plays a critical role in mitosis as it mediates centrosome separation and bipolar spindle assembly and maintenance. Inhibition of KSP function leads to cell cycle arrest at mitosis with the formation of monoastral microtubule arrays, and ultimately, to cell death. Several KSP inhibitors are currently...

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Asymmetric Division: A Kinesin for Spindle Positioning

The meiotic spindles of animal eggs move to extremely asymmetric positions, close to the cell cortex. A recent paper has identified a motor complex that may move the meiotic spindle toward the cortex in Caenorhabditis elegans eggs.

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ژورنال

عنوان ژورنال: Annals of Oncology

سال: 2018

ISSN: 0923-7534

DOI: 10.1093/annonc/mdy046.019