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Other names | JNJ-26481585 |
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Bioavailability | oral [1] |
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Chemical and physical data | |
Formula | C21H26N6O2 |
Molar mass | 394.479 g·mol−1 |
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Quisinostat (USAN; [2] development code JNJ-26481585) is an experimental drug candidate for the treatment of cancer. It is a "second generation" histone deacetylase inhibitor with antineoplastic activity. [3] [4] [5] It is highly potent against class I and II HDACs. [6]
It was developed by Janssen Pharmaceuticals and licensed to NewVac LLC. [7]
Preclinical studies show that quisinostat amplifies HDAC-repressed expression of E-cadherin, leading to a reversal of epithelial to mesenchymal transition in tumor cells. [7]
Results of a phase I trials in patients with multiple myeloma in combination with bortezomib and dexamethasone were published in 2016. [8]
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include hypercalcemia and amyloidosis.
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.
Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is generally used together with other medications. It is given by injection.
Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins. They are being studied in the treatment of cancer; three are approved for use in treating multiple myeloma.
Plitidepsin is a chemical compound extracted from the ascidian Aplidium albicans. It is currently undergoing clinical trial testing. It is a member of the class of compounds known as didemnins.
Vorinostat (rINN) also known as Suberoylanilide hydroxamic acid is a member of a larger class of compounds that inhibit histone deacetylases (HDAC). Histone deacetylase inhibitors (HDI) have a broad spectrum of epigenetic activities.
Histone deacetylase inhibitors are chemical compounds that inhibit histone deacetylases.
TopoTarget was a Copenhagen-based biotechnology company focused on the discovery and development of drugs and therapies to treat cancer. In 2014, it merged with BioAlliance Pharma and is now part of Onxeo.
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.
Pomalidomide, sold under the brand names Pomalyst and Imnovid, is an anti-cancer medication used for the treatment of multiple myeloma and AIDS-related Kaposi sarcoma.
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.
Carfilzomib, sold under the brand name Kyprolis, is an anti-cancer medication acting as a selective proteasome inhibitor. Chemically, it is a tetrapeptide epoxyketone and an analog of epoxomicin. It was developed by Onyx Pharmaceuticals.
Givinostat (INN) or gavinostat is a histone deacetylase inhibitor with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities. It is a hydroxamic acid used in the form of its hydrochloride.
Daratumumab, sold under the brand name Darzalex, is an anti-cancer monoclonal antibody medication. It binds to CD38, which is overexpressed in multiple myeloma cells. Daratumumab was originally developed by Genmab, but it is now being jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, which acquired worldwide commercialization rights to the drug from Genmab.
Abexinostat is an experimental drug candidate for cancer treatment. It was developed by Pharmacyclics and licensed to Xynomic. and is in Phase II clinical trials for B-cell lymphoma. Pre-clinical study suggests the potential for treatment of different types of cancer as well.
Filanesib is a kinesin spindle protein (KIF11) inhibitor which has recently been proposed as a cancer treatment, specifically for multiple myeloma.
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.
Isatuximab, sold under the brand name Sarclisa, is a monoclonal antibody (mAb) medication for the treatment of multiple myeloma.
Selinexor sold under the brand name Xpovio among others, is a selective inhibitor of nuclear export used as an anti-cancer medication. It works by blocking the action of exportin 1 and thus blocking the transport of several proteins involved in cancer-cell growth from the cell nucleus to the cytoplasm, which ultimately arrests the cell cycle and leads to apoptosis. It is the first drug with this mechanism of action.