Vorinostat (rINN) or suberoylanilide hydroxamic acid (SAHA), is a drug currently under investigation for the treatment of cutaneous T cell lymphoma (CTCL). Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II) at nanomolar concentrations (IC50< 86 nM). These enzymes catalyze the removal of acetyl groups from the lysine residues of histones proteins. In some cancer cells, there is an overexpression of HDACs, or an aberrant recruitment of HDACs to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones. By inhibiting histone deacetylase, vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of vorinostat has not been fully characterized. Vorinostat is used for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat is marketed under the name Zolinza by Merck for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) when the disease persists, gets worse, or comes back during or after two systemic therapies.

Acetaminophen, also known as paracetamol, is commonly used for its analgesic and antipyretic effects. Its therapeutic effects are similar to salicylates, but it lacks anti-inflammatory, antiplatelet, and gastric ulcerative effects. Acetaminophen (USAN) or Paracetamol (INN) is a widely used analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. It is a major ingredient in numerous cold and flu medications and many prescription analgesics. It is extremely safe in standard doses, but because of its wide availability, deliberate or accidental overdoses are not uncommon. Acetaminophen, unlike other common analgesics such as aspirin and ibuprofen, has no anti-inflammatory properties or effects on platelet function, and it is not a member of the class of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. At therapeutic doses, acetaminophen does not irritate the lining of the stomach nor affect blood coagulation, kidney function, or the fetal ductus arteriosus (as NSAIDs can). Acetaminophen is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDs, acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects. Acetaminophen indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why acetaminophen is effective in the central nervous system and in endothelial cells but not in platelets and immune cells, which have high levels of peroxides. Studies also report data suggesting that acetaminophen selectively blocks a variant of the COX enzyme that is different from the known variants COX-1 and COX-2. This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, but future research may provide further insight into how it works. The antipyretic properties of acetaminophen are likely due to direct effects on the heat-regulating centers of the hypothalamus resulting in peripheral vasodilation, sweating and hence heat dissipation.

CG-200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed by CrystalGenomics, Inc for treatment of various hematological and solid cancers. Combinations of CG-200745 with SN38 (the active form of irinotecan), or oxaliplatin were more effective than the agents alone when used to inhibit the growth of HCT116 cells. The protein expressions of acetyl-H3, p21, caspase-3, -8, and -9, PARP, and XIAP were affected in a time- and dose-dependent manner in HCT116 cells treated with the CG-200745 alone or combined CG-200745 and SN-38. In HCT116 xenografts, the HDACI CG-200745 in combination with irinotecan dramatically inhibited tumor growth without showing additive toxicity.

Quisinostat is an orally bioavailable potent histone deacetylase inhibitor, specifically selected due to its sustained inhibition of HDAC1 in solid tumor tissues and prolonged period of half-elimination from tissues. Phase 2 clinical trials are ongoing in patients with platinum-resistant ovarian cancer and non-small cell lung cancer (NSCLC). Quisinostat is active in the treatment of patients with relapsed or refractory Sézary syndrome. The most common drug-related adverse events reported in this trial were: nausea, diarrhea, asthenia. Grade 3 adverse events were also reported: hypertension, lethargy and pruritus.