Histone deacetylases (EC 3.5.1.98, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. HDAC's action is opposite to that of histone acetyltransferase. HDAC proteins are now also called lysine deacetylases (KDAC), to describe their function rather than their target, which also includes non-histone proteins. In general, they suppress gene expression.
Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell. It is a form of unsealed source radiotherapy. In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells. The ability for the antibody to specifically bind to a tumor-associated antigen increases the dose delivered to the tumor cells while decreasing the dose to normal tissues. By its nature, RIT requires a tumor cell to express an antigen that is unique to the neoplasm or is not accessible in normal cells.
Tipifarnib is a farnesyltransferase inhibitor. Farnesyltransferase inhibitors block the activity of the farnesyltransferase enzyme by inhibiting prenylation of the CAAX tail motif, which ultimately prevents Ras from binding to the membrane, rendering it inactive.
Epratuzumab is a humanized monoclonal antibody. Potential uses may be found in oncology and in treatment of inflammatory autoimmune disorders, such as systemic lupus erythematosus (SLE).
Acute myeloblastic leukemia with maturation (M2) is a subtype of acute myeloid leukemia (AML).
Histone deacetylase inhibitors are chemical compounds that inhibit histone deacetylases. Since deacetylation of histones produces transcriptionally silenced heterochromatin, HDIs can render chromatin more transcriptionally active and induce epigenomic changes.
Histone deacetylase 8 is an enzyme that in humans is encoded by the HDAC8 gene.
Panobinostat, sold under the brand name Farydak, is a medication used for the treatment of multiple myeloma. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor.
Romidepsin, sold under the brand name Istodax, is an anticancer agent used in cutaneous T-cell lymphoma (CTCL) and other peripheral T-cell lymphomas (PTCLs). Romidepsin is a natural product obtained from the bacterium Chromobacterium violaceum, and works by blocking enzymes known as histone deacetylases, thus inducing apoptosis. It is sometimes referred to as depsipeptide, after the class of molecules to which it belongs. Romidepsin is branded and owned by Gloucester Pharmaceuticals, a part of Celgene.
Mocetinostat (MGCD0103) is a benzamide histone deacetylase inhibitor undergoing clinical trials for treatment of various cancers including follicular lymphoma, Hodgkin's lymphoma and acute myelogenous leukemia.
Phosphoinositide 3-kinase inhibitors are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable.
Ocaratuzumab is a humanized monoclonal antibody designed for the treatment of cancer and autoimmune disorders. The antibody is engineered for enhanced affinity to the CD20 antigen on B-lymphocytes, increased antibody-dependent cell-mediated cytotoxicity (ADCC), and for improved treatment of low-affinity FcγRIIIa allotypes.
Quisinostat is an experimental drug candidate for the treatment of cancer. It is a "second generation" histone deacetylase inhibitor with antineoplastic activity. It is highly potent against class I and II HDACs.
Pracinostat (SB939) is an orally bioavailable, small-molecule histone deacetylase (HDAC) inhibitor based on hydroxamic acid with potential anti-tumor activity characterized by favorable physicochemical, pharmaceutical, and pharmacokinetic properties.
Resminostat is an orally bioavailable inhibitor of histone deacetylases (HDACs), of which inhibitors are antineoplastic agents.
Tucidinostat is a histone deacetylase inhibitor (HDI) developed in China. It was also known as HBI-8000. It is a benzamide HDI and inhibits Class I HDAC1, HDAC2, HDAC3, as well as Class IIb HDAC10.
Pevonedistat (MLN4924) is a selective NEDD8 inhibitor. It is being investigated as a cancer treatment, e.g. for mantle cell lymphoma (MCL).
Pirtobrutinib, sold under the brand name Jaypirca, is an anticancer medication that is used to treat mantle cell lymphoma. It inhibits B cell lymphocyte proliferation and survival by binding and inhibiting Bruton's tyrosine kinase (BTK). It is taken by mouth.
Zabadinostat is an experimental epigenetic drug being investigated as a potential treatment for advanced or metastatic cancers. It is an orally available Class I selective histone deacetylase (HDAC) inhibitor, with half maximal inhibitory concentrations (IC50) of 62 nM, 570 nM and 550 nM, against HDAC1, HDAC2 and HDAC3, respectively. It shows no activity against HDAC class II.
Avadomide is an experimental cereblon E3 ligase modulator, or thalidomide analog studied to see if it is effective against cancer.
