960058-93-9Relevant articles and documents
Identifying drug targets in tissues and whole blood with thermal-shift profiling
Bantscheff, Marcus,Becher, Isabelle,Bergamini, Giovanna,Childs, Dorothee D.,Eberl, H. Christian,Faelth-Savitski, Maria,Franken, Holger,Heller, Bianca,Huber, Wolfgang,Kalxdorf, Mathias,Krause, Jana,Kurzawa, Nils,Perrin, Jessica,Poeckel, Daniel,Rau, Christina E.,Rutkowska, Anna,Savitski, Mikhail M.,Sevin, Daniel C.,Stonehouse, Eugenia,Strohmer, Katrin,Thomson, Douglas W.,Vappiani, Johanna,Werner, Thilo
, (2020)
Monitoring drug–target interactions with methods such as the cellular thermal-shift assay (CETSA) is well established for simple cell systems but remains challenging in vivo. Here we introduce tissue thermal proteome profiling (tissue-TPP), which measures
Design of Hydrazide-Bearing HDACIs Based on Panobinostat and Their p53 and FLT3-ITD Dependency in Antileukemia Activity
Li, Xiaoyang,Jiang, Yuqi,Peterson, Yuri K.,Xu, Tongqiang,Himes, Richard A.,Luo, Xin,Yin, Guilin,Inks, Elizabeth S.,Dolloff, Nathan,Halene, Stephanie,Chan, Sherine S. L.,Chou, C. James
, p. 5501 - 5525 (2020/06/10)
Here, we present a new series of hydrazide-bearing class I selective HDAC inhibitors designed based on panobinostat. The cap, linker, and zinc-binding group were derivatized to improve HDAC affinity and antileukemia efficacy. Lead inhibitor 13a shows picomolar or low nanomolar IC50 values against HDAC1 and HDAC3 and exhibits differential toxicity profiles toward multiple cancer cells with different FLT3 and p53 statuses. 13a indirectly inhibits the FLT3 signaling pathway and down-regulates master antiapoptotic proteins, resulting in the activation of pro-caspase3 in wt-p53 FLT3-ITD MV4-11 cells. While in the wt-FLT3 and p53-null cells, 13a is incapable of causing apoptosis at a therapeutic concentration. The MDM2 antagonist and the proteasome inhibitor promote 13a-triggered apoptosis by preventing p53 degradation. Furthermore, we demonstrate that apoptosis rather than autophagy is the key contributing factor for 13a-triggered cell death. When compared to panobinostat, 13a is not mutagenic and displays superior in vivo bioavailability and a higher AUC0-inf value.
HISTONE DEACETYLASE INHIBITORS AND USES THEREOF
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Page/Page column 34; 35, (2018/04/27)
Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of cancer.
