Literature DB >> 19344997

Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges.

Peter Atadja1.   

Abstract

The histone deacetylase (HDAC) inhibitors are emerging as a highly useful class of anticancer agents that inhibit the enzyme HDAC involved in the deacetylation of histone and non-histone cellular proteins. The HDAC inhibitor, panobinostat (LBH589, Novartis Pharmaceuticals), achieves potent inhibition of all HDAC enzymes implicated in cancer and has demonstrated potent anti-tumor activity in preclinical models and promising clinical efficacy in cancer patients. In this review we discuss the successes and challenges surrounding the development of panobinostat, focusing on its proposed mechanism of action, preclinical anti-tumor activity, and early clinical efficacy in hematologic and solid tumors.

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Year:  2009        PMID: 19344997     DOI: 10.1016/j.canlet.2009.02.019

Source DB:  PubMed          Journal:  Cancer Lett        ISSN: 0304-3835            Impact factor:   8.679


  153 in total

1.  The HDAC inhibitor LBH589 (panobinostat) is an inhibitory modulator of aromatase gene expression.

Authors:  Shiuan Chen; Jingjing Ye; Ikuko Kijima; Dean Evans
Journal:  Proc Natl Acad Sci U S A       Date:  2010-06-01       Impact factor: 11.205

Review 2.  Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma.

Authors:  Teru Hideshima; Paul G Richardson; Kenneth C Anderson
Journal:  Mol Cancer Ther       Date:  2011-11       Impact factor: 6.261

3.  Thermal proteome profiling for unbiased identification of direct and indirect drug targets using multiplexed quantitative mass spectrometry.

Authors:  Holger Franken; Toby Mathieson; Dorothee Childs; Gavain M A Sweetman; Thilo Werner; Ina Tögel; Carola Doce; Stephan Gade; Marcus Bantscheff; Gerard Drewes; Friedrich B M Reinhard; Wolfgang Huber; Mikhail M Savitski
Journal:  Nat Protoc       Date:  2015-09-17       Impact factor: 13.491

4.  Design of Hydrazide-Bearing HDACIs Based on Panobinostat and Their p53 and FLT3-ITD Dependency in Antileukemia Activity.

Authors:  Xiaoyang Li; Yuqi Jiang; Yuri K Peterson; Tongqiang Xu; Richard A Himes; Xin Luo; Guilin Yin; Elizabeth S Inks; Nathan Dolloff; Stephanie Halene; Sherine S L Chan; C James Chou
Journal:  J Med Chem       Date:  2020-05-06       Impact factor: 7.446

Review 5.  Panobinostat: first global approval.

Authors:  Karly P Garnock-Jones
Journal:  Drugs       Date:  2015-04       Impact factor: 9.546

Review 6.  Population and target considerations for triple-negative breast cancer clinical trials.

Authors:  Terry Hyslop; Yvonne Michael; Tiffany Avery; Hallgeir Rui
Journal:  Biomark Med       Date:  2013-02       Impact factor: 2.851

Review 7.  Clinically Applicable Inhibitors Impacting Genome Stability.

Authors:  Anu Prakash; Juan F Garcia-Moreno; James A L Brown; Emer Bourke
Journal:  Molecules       Date:  2018-05-13       Impact factor: 4.411

8.  Suppression of triple-negative breast cancer metastasis by pan-DAC inhibitor panobinostat via inhibition of ZEB family of EMT master regulators.

Authors:  Lyndsay V Rhodes; Chandra R Tate; H Chris Segar; Hope E Burks; Theresa B Phamduy; Van Hoang; Steven Elliott; Diari Gilliam; F Nell Pounder; Muralidharan Anbalagan; Douglas B Chrisey; Brian G Rowan; Matthew E Burow; Bridgette M Collins-Burow
Journal:  Breast Cancer Res Treat       Date:  2014-05-09       Impact factor: 4.872

9.  The pan-deacetylase inhibitor panobinostat modulates the expression of epithelial-mesenchymal transition markers in hepatocellular carcinoma models.

Authors:  Pietro DI Fazio; Roberta Montalbano; Karl Quint; Beate Alinger; Ralf Kemmerling; Tobias Kiesslich; Matthias Ocker; Daniel Neureiter
Journal:  Oncol Lett       Date:  2012-10-01       Impact factor: 2.967

10.  Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model.

Authors:  Holly A F Stessman; Linda B Baughn; Aaron Sarver; Tian Xia; Raamesh Deshpande; Aatif Mansoor; Susan A Walsh; John J Sunderland; Nathan G Dolloff; Michael A Linden; Fenghuang Zhan; Siegfried Janz; Chad L Myers; Brian G Van Ness
Journal:  Mol Cancer Ther       Date:  2013-03-27       Impact factor: 6.261

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