Identification of the key structural elements of a dihydropyrimidinone core driving toward more potent Hsp90 C-terminal inhibitors.
نویسندگان
چکیده
Hsp90 C-terminal modulation represents an attractive strategy for the development of potent and safer antitumor compounds. Continuing our investigation on DHPM type inhibitors here we report a new set of potent C-terminal ligands which allowed us to identify the key structural features crucial for the biological activity.
منابع مشابه
Targeting the Hsp90 C-terminal domain by the chemically accessible dihydropyrimidinone scaffold.
Hsp90 C-terminal ligands are potential new anti-cancer drugs alternative to the more studied N-terminal inhibitors. Here we report the identification of a new dihydropyrimidinone binding the C-terminus, which is not structurally related to other well-known natural and nature-inspired inhibitors of this second druggable Hsp90 site.
متن کاملTriazole Containing Novobiocin and Biphenyl Amides as Hsp90 C-Terminal Inhibitors.
Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is a major detriment associated with Hsp90 N-terminal inhibitors under clinical investigation. Based upon prior SAR trends, a 1,2,3-triazole side chain was placed in lieu of the ...
متن کاملPharmacological and genetic analysis of 90-kDa heat shock isoprotein-aryl hydrocarbon receptor complexes.
The 90-kDa heat shock protein (Hsp90) is an abundant chaperone that regulates a diverse set of intracellular signaling proteins. Drugs that inhibit Hsp90 activity have been useful in the identification of novel Hsp90-dependent signaling pathways. One class of inhibitory compounds disrupts Hsp90-dependent processes by binding to the N-terminal ATPase/p23-binding domain of Hsp90, whereas a second...
متن کاملBlast Mitigation Analysis of Semi-Buried Structure
Semi-buried structures are most commonly used at first line of defense along the border between two countries. This demands investigation of their dynamic behaviour under blast loading. Herein, a semi-buried structure with foam sandwiched walls and buttresses to reduce the effect of blast is analysed. The effect of provision of different configurations of buttresses and foam core between two la...
متن کاملشناسایی و اولویتبندی عوامل کلیدی در پیادهسازی معنویت سازمانی: مطالعه موردی کتابخانههای عمومی شهر یزد
Purpose: This research aims to identify and prioritize factors affecting organizational spirituality in public libraries of Yazd city in Iran. Methodology: The present work is an applied research. We used survey method for data collection and analysis and our tool was a researcher-made questionnaire. The research sample of the work can be divided in two parts. In part one, we chose 111 public ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Chemical communications
دوره 52 87 شماره
صفحات -
تاریخ انتشار 2016