Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents
Top Cited Papers
Open Access
- 2 March 2015
- Vol. 20 (3), 3898-3941
- https://doi.org/10.3390/molecules20033898
Abstract
Histone dacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones and regulate expression of tumor suppressor genes. They are implicated in many human diseases, especially cancer, making them a promising therapeutic target for treatment of the latter by developing a wide variety of inhibitors. HDAC inhibitors interfere with HDAC activity and regulate biological events, such as cell cycle, differentiation and apoptosis in cancer cells. As a result, HDAC inhibitor-based therapies have gained much attention for cancer treatment. To date, the FDA has approved three HDAC inhibitors for cutaneous/peripheral T-cell lymphoma and many more HDAC inhibitors are in different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. In the intensifying efforts to discover new, hopefully more therapeutically efficacious HDAC inhibitors, molecular modeling-based rational drug design has played an important role in identifying potential inhibitors that vary in molecular structures and properties. In this review, we summarize four major structural classes of HDAC inhibitors that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.Keywords
This publication has 199 references indexed in Scilit:
- A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: A gynecologic oncology group studyGynecologic Oncology, 2012
- Histone deacetylase inhibitors (HDACIs). Structure—activity relationships: history and new QSAR perspectivesMedicinal Research Reviews, 2011
- Design, Synthesis, Docking, and Biological Evaluation of Novel Diazide-Containing Isoxazole- and Pyrazole-Based Histone Deacetylase ProbesJournal of Medicinal Chemistry, 2011
- Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS)Annals of Hematology, 2011
- The sirtuin pathway in ageing and Alzheimer disease: mechanistic and therapeutic considerationsThe Lancet Neurology, 2011
- Phase I clinical, pharmacokinetic and pharmacodynamic study of SB939, an oral histone deacetylase (HDAC) inhibitor, in patients with advanced solid tumoursBritish Journal of Cancer, 2011
- On the inhibition of histone deacetylase 8Bioorganic & Medicinal Chemistry, 2010
- Phase II trial of the histone deacetylase inhibitor belinostat in women with platinum resistant epithelial ovarian cancer and micropapillary (LMP) ovarian tumoursEuropean Journal of Cancer, 2010
- Chromatin Modifications and Their FunctionCell, 2007
- Thioredoxin in cancer—Role of histone deacetylase inhibitorsSeminars in Cancer Biology, 2006