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21.
Light‐Controlled Histone Deacetylase (HDAC) Inhibitors: Towards Photopharmacological Chemotherapy
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Dr. Wiktor Szymanski Maria E. Ourailidou Dr. Willem A. Velema Prof. Dr. Frank J. Dekker Prof. Dr. Ben L. Feringa 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(46):16517-16524
Cancer treatment suffers from limitations that have a major impact on the patient’s quality of life and survival. In the case of chemotherapy, the systemic distribution of cytotoxic drugs reduces their efficacy and causes severe side effects due to nonselective toxicity. Photopharmacology allows a novel approach to address these problems because it employs external, local activation of chemotherapeutic agents by using light. The development of photoswitchable histone deacetylase (HDAC) inhibitors as potential antitumor agents is reported herein. Analogues of the clinically used chemotherapeutic agents vorinostat, panobinostat, and belinostat were designed with a photoswitchable azobenzene moiety incorporated into their structure. The most promising compound exhibits high inhibitory potency in the thermodynamically less stable cis form and a significantly lower activity for the trans form, both in terms of HDAC activity and proliferation of HeLa cells. This approach offers a clear prospect towards local photoactivation of HDAC inhibition to avoid severe side effects in chemotherapy. 相似文献
22.
Shi Xunqing Wang Zhiping John HL Pang Zhang Xueren Nie Jingxu 《Acta Mechanica Sinica》2002,18(3):274-287
In this study, a new unified creep constitutive relation and a modified energy-based fatigue model have been established respectively
to describe the creep flow and predict the fatigue life of Sn−Pb solders. It is found that the relation successfully elucidates
the creep mechanism related to current constitutive relations. The model can be used to describe the temperature and frequency
dependent low cycle fatigue behavior of the solder. The relation and the model are further employed in part II to develop
the numerical simulation approach for the long-term reliability assessment of the plastic ball grid array (BGA) assembly.
The project supported by the National Natural Science Foundation of China (59705008) 相似文献
23.
Hedberg C Dekker FJ Rusch M Renner S Wetzel S Vartak N Gerding-Reimers C Bon RS Bastiaens PI Waldmann H 《Angewandte Chemie (International ed. in English)》2011,50(42):9832-9837
A matter of common sense: A common recognition motif consisting of a negatively charged group five to six bonds away (red) from the (thio)ester functionality (green) and a positively charged tail group ten to twelve bonds away (blue) was identified in two native acyl protein thioesterase?1 (APT1) substrates. This similarity led to the design of potent inhibitors of the Ras-depalmitoylating enzyme APT1. 相似文献
24.
H. Dekker 《Physics letters. A》1982,88(6):279-281
The master equation for diffusion in a bistable potential is evaluated systematically in terms of the small-noise parameter for the case where the system is initially at the unstable state. The expansion is valid for all times, that is in the initial and intermediate as well as in the final regime. The theory does not involve free fitting parameters and is easily generalized to more complicated processes. 相似文献
25.
This paper gives a negative result onBSI-stability for the Lobatto IIIC-methods with more than two stages. We also give a necessary condition forBSI-stability. 相似文献
26.
27.
K. Dekker 《BIT Numerical Mathematics》1984,24(3):347-356
In the implementation of implicit Runge-Kutta methods inaccuracies are introduced due to the solution of the implicit equations. It is shown that these errors can be bounded independently of the stiffness of the differential equation considered if a certain condition is satisfied. This condition is also sufficient for the existence and uniqueness of a solution to the algebraic equations. TheBSI-andBS-stability properties of several classes of implicit methods are established. 相似文献
28.
29.
H. Dekker 《Physics letters. A》1980,80(5-6):369-371
30.
It is shown how a fairly simple random walk on a lattice provides insight into the nature of hydrodynamic boundary conditions. In a flow parallel to the boundary, collisions of up and downward moving particles induce lateral bulk diffusion. At the wall the model accounts essentially for 1) specular reflection, 2) diffuse reflection and 3) trapping at the surface. The steady state is solved exactly. In the continuum limit the case of stick versus slip boundary conditions is explained in its relation to the interplay of bulk and boundary processes. 相似文献