71995-34-1Relevant academic research and scientific papers
Mechanistic insights into binding of ligands with thiazolidinedione warhead to human histone deacetylase 4
Basheer, Sidra,J?nsch, Niklas,Müller, Marlene,Meyer-Almes, Franz-Josef,Ramaa, C. S.,Schweipert, Markus,Tilekar, Kalpana,Upadhyay, Neha,Wozny, Ewelina,Wurster, Eva
, (2021/10/26)
Recently, we have reported that non-hydroxamate thiazolidinedione (TZD) analogs are capable of inhibiting human deacetylase 4 (HDAC4). This study aims at the dissection of the molecular determinants and kinetics of the molecular recognition of TZD ligands by HDAC4. For this purpose, a structure activity relationship analysis of 225 analogs was combined with a comprehensive study of the enzyme and binding kinetics of a variety of HDAC4 mutant variants. The experimental data were rationalized by docking to the two major conformations of HDAC4. TZD ligands are competitive inhibitors and bind via a two-step mechanism involving principal molecular recognition and induced fit. The residence time of 24 g is (34 ± 3) min and thus much larger than that of the canonical pan-HDAC inhibitor SAHA ((5 ± 2) min). Importantly, the binding kinetics can be tuned by varying the structure of the CAP group.
Permuted 2,4-thiazolidinedione (TZD) analogs as GLUT inhibitors and their in-vitro evaluation in leukemic cells
Aguilera, Renato J.,Choe, Jun-yong,Hess, Jessica D.,Iancu, Cristina V.,Macias, Lucasantiago Henze,Meyer-Almes, Franz-Josef,Mrowka, Piotr,Ramaa, C. S.,Schweipert, Markus,Tilekar, Kalpana,Upadhyay, Neha
, (2020/08/21)
Cancer is a heterogeneous disease, and its treatment requires the identification of new ways to thwart tumor cells. Amongst such emerging targets are glucose transporters (GLUTs, SLC2 family), which are overexpressed by almost all types of cancer cells; t
