146305-29-5Relevant articles and documents
Synthesis, characterization of novel coupling products and 4-arylhydrazono-2-pyrazoline-5-ones as potential antimycobacterial agents
Kuecuekguezel, S. Gueniz,Rollas, Sevim
, p. 583 - 588 (2002)
Novel coupling products 7a-d and 4-arylhydrazono-2-pyrazoline-5-ones 8a-e were synthesized and evaluated for antimycobacterial activity against Mycobacterium tuberculosis H37Rv and Mycobacterium avium. Compound 7b was found to be the most potent derivatives of the 7a-d series by an MIC value of 6.25 μg/ml.
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.
Development of novel Asf1-H3/H4 inhibitors
Miknis, Greg F.,Stevens, Sarah J.,Smith, Luke E.,Ostrov, David A.,Churchill, Mair E.A.
supporting information, p. 963 - 968 (2015/02/19)
The histone chaperone anti-silencing function 1 (Asf1) has emerged as a promising target for therapeutic intervention for multiple cancers (Cell 2006, 127, 458). Asf1 is involved in the packaging of the eukaryotic genome into chromatin, which is essential