HDAC1:2-containing complex binds HDAC2 Inhibitors

Stable Identifier
Reaction [binding]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
To carry out gene expression, a cell must control the winding and unwinding of DNA around histones. This is mediated by histone acetyl transferases (HATs) and histone deacetylases (HDACs). HDAC inhibitors inhibit the proliferation of tumour cells by inducing cell cycle arrest, differentiation and/or apoptosis (Zhang et al. 2019). Belinostat (Marks et al. 2000, O'Connor et al. 2015), vorinostat (Marks & Breslow 2007) and romidepsin (Ueda et al. 1994, VanderMolen et al. 2011) are HDAC inhibitors approved for the treatment of Peripheral T-cell lymphomas (PTCLs) (Hood & Shah 2016). These drugs are believed to bind to many, if not all HDAC proteins.

Human papillomaviruses (HPVs) cause epithelial proliferative diseases. The HDAC inhibitors vorinostat, belinostat and panobinostat have been shown to inhibit HPV DNA amplification and cause apoptosis in preclinical experiments (Banerjee et al. 2018).

The antiepileptic drug valproic acid inhibits HDAC2 and therefore is a promising drug for cancer therapy (Göttlicher et al. 2001).
Literature References
PubMed ID Title Journal Year
17211407 Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug

Marks, PA, Breslow, R

Nat. Biotechnol. 2007
7513682 FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity

Fujita, T, Okuhara, M, Ueda, H, Nishimura, M, Nakajima, H, Hori, Y, Goto, T

J. Antibiot. 1994
21587264 Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma

VanderMolen, KM, McCulloch, W, Oberlies, NH, Pearce, CJ

J. Antibiot. 2011
10922406 Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells

Marks, PA, Rifkind, RA, Richon, VM

J. Natl. Cancer Inst. 2000
11742974 Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells

Sleeman, JP, Zhu, P, Göttlicher, M, Lo Coco, F, Minucci, S, Krämer, OH, Schimpf, A, Pelicci, PG, Nervi, C, Heinzel, T, Giavara, S

EMBO J 2001
26101246 Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study

Doorduijn, J, Foss, F, Masszi, T, Savage, K, Shustov, A, Van Hoof, A, O'Connor, OA, Brown, P, Horwitz, S, Bhat, G, Jurczak, W, Allen, LF, Chawla, S, Hess, G, Knoblauch, P, Choi, MR, Walewski, J

J. Clin. Oncol. 2015
Orthologous Events
Cite Us!