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Vorinostat CAS 149647-78-9

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  • Appearance: White powder
  • Assay: 99. 0%min
  • Stock: In stock
  • Sample: Available
  • Zhishang Chemical: Vorinostat Supplier & Manufacturer

Basic Info

What is Vorinostat?

Vorinostat is a histone deacetylase prevention (HDACI), which can up-regulate growth suppressor genes by interfering with the activity of sirtone deacetylase, block lump cell development and cause tumor cell selection. function of apoptosis. Vorinostat was approved by the United States FDA on October 6, 2006 for the therapy of peripheral cutaneous T-cell lymphoma (cutaneous T-cell lymphoma) with significant skin invasion that has actually advanced, drug-resistant or relapsed after 2 systemic regimens., CTCL) In recent years, with the continual growing of study, vorinostat has actually likewise shown excellent therapeutic results in the treatment of various other tumors and help.

On October 6, 2006, the United State Fda (FDA) authorized vorinostat capsules (vorinostat) as a new medication for the treatment of skin cancer cells. The drug is the world’s very first new anticancer medication that inhibits histone deacetylase developed by Merck of the United States, and also is made use of to treat cutaneous T-cell lymphoma (CTCL). Metastatic cutaneous T-lymphocytoma that still can not be cured, or worsens, or regressions. A multitude of experimental research studies and also scientific outcomes show that vorinostat has good medicinal impact on a variety of lumps, and it has evident collaborating impact with other lump drugs. Currently, the study on the treatment of various other lumps is still in-depth. market potential customers. Proof for the safety and also efficiency of vorinostat originates from two scientific trials involving 107 CTCL individuals who had fallen back after getting various other medicines. According to the standard evaluation established by the improvement of the skin sore score quality, 30% of patients that obtained Zolinza enhanced, and also the result lasted for an average of 168 days. One of the most common serious negative responses were pulmonary embolism, dehydration, deep blood vessel apoplexy, as well as anemia. Common damaging responses were intestinal symptoms (consisting of looseness of the bowels, queasiness, decreased appetite, throwing up, and irregularity); exhaustion, cools, and dysgeusia. The outcomes of animal experiments reveal that the medicine is contraindicated for expecting ladies.

Vorinostat Uses

Vorinostat has inhibitory task against histone deacetylase (HDAC) 1/2/3 (kind I) and also HDAC6 (kind II), enzymes that catalyze the deacetylation of tyrosine deposits in histones and also transcription elements. In some cancer cells, there is overexpression of HDACs or aberrant gathering of HDACs in oncogenic transcription elements, causing hypoacetylation of core nucleosomal histones. Histone hypoacetylation is connected with condensation of chromatin structure and suppression of genetics transcription. Restraint of HDAC activity leads to the accumulation of acetyl groups on histone tyrosine deposits, resulting in depolymerization of chromatin framework and activation of transcription. In artificial insemination researches, vorinostat caused aggregation of acetylated histones as well as cell cycle apprehension and/or apoptosis in some mutant cells. However, the antitumor device of vorinostat has actually not yet been fully understood.

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Application of Vorinostat

CTCL is a type of lymphoma that begins as a lesion in the skin and then spreads to the lymphatic system or other organs. The cause of CTCL is currently unclear, and it may be related to chronic and long-term exposure to chemicals in the environment, such as “pesticides”. Epidemiology shows that the disease mostly occurs in adults aged 40 to 60, with a male-to-female ratio of about 2:1, and the attack rate increases with age.

There are 2 main phenotypes of CTCL: one is erythroderma and the other is mycosis fungoides. Vorinostat can treat CTCL by inducing cell differentiation, blocking cell cycle, and inducing cell regulation. Vorinostat has been approved by the US FDA in 2006 for the treatment of CTCL that has exacerbated, persisted, and relapsed or has not responded to 2 systemic agents. Anderson Cancer Center conducted a Phase II clinical study on vorinostat, mainly to observe the efficacy, safety and tolerability of vorinostat in patients with refractory CTCL.

Patients over 18 years old who were refractory or resistant to conventional chemotherapy and expected to survive for more than 3 months were divided into three groups. Group 1 was given vorinostat 400 mg· d – 1, the intermittent period was changed to 300 mg/d, and the average treatment time was 12 weeks; the patients in the second group were given 300 mg/time – 1, bid, 3 days a week, and the average treatment time was 7 weeks; the patients in the third group were given 300 mg/d mg/time, bid, the average treatment time is 7 weeks.

After the study, the effective rate of each group was observed. The effective rate of the first group was 31%, that of the second group was 9.1%, and that of the third group was 33.3%. The effective rates of the first group and the third group were significantly higher than those of the second group . Seven of 33 patients received vorinostat for 23 weeks or longer, including 4 in group 1, 1 in group 2, and 2 in group 3. In terms of pruritus symptom relief, 73% in group 1 were relieved, compared with 18% in group 2 and 44% in group 3.

In terms of safety and adverse reactions, the most common adverse reactions included fatigue (78%), diarrhea (60%), nausea (60%), thrombocytopenia (54%), taste disturbance (51%), dry mouth (38%) % ), although there was no significant difference in the incidence of adverse reactions among the 3 groups, 41.7% of patients in group 3 experienced grade 3-4 thrombocytopenia, while only 7.7% and 8.3% of patients in groups 1 and 3 Grade 3-4 thrombocytopenia.

In the laboratory study of the combination of HDAC inhibitor vorinostat and PARP inhibitor PJ34 on leukemia cells, they were divided into 3 groups, namely vorinostat group, PJ34 group and two-drug combination group. Into HL60, MOLT4, U937, K562 cell culture medium for culture, evaluate cell proliferation, apoptosis, mitochondrial membrane potential and cell cycle. The results showed that the PJ34 group had no effect on cell growth, while the vorinostat group decreased cell proliferation, decreased mitochondrial membrane potential, and increased the percentage of apoptotic cells.

The combination of the two drugs can further reduce the proliferation of HL60, MOLT4 and K562 cells, increase their apoptosis, and weaken the mitochondrial membrane potential, but has no effect on U937 cells. This result shows that vorinostat can inhibit the proliferation of myeloid leukemia strains in vitro.

Studies have found that vorinostat and carfilzomib have synergistic effects on T-lymphoblastic leukemia cells. Carfilzomib is a proteasome inhibitor and vorinostat is a histone deacetylase inhibitor. In this study, lethal concentrations of carfilzomib and low concentrations of vorinostat acted on T lymphocyte leukemia cells exposed to carbon monoxide, and the leukemia cells underwent apoptosis, reactive oxygen species (ROS) increased sharply, and mitochondrial membrane potential ( MMP) was significantly reduced, cytochrome c release was increased, caspase-9 and -3 activation was enhanced, and PARP kinase cleavage. Furthermore, the combination blocked the G2-M phase of leukemia cells. These results indicate that carfilzomib and vorinostat have a clear synergistic effect on T-lymphoblastic leukemia cell lines.

Multiple myeloma, the most common type of malignant plasma cell disease, is characterized by the malignant proliferation of monoclonal plasma cells and the secretion of large amounts of monoclonal immunoglobulin. The role of vorinostat as a sirtuin inhibitor in the treatment of multiple relapsed multiple myeloma has gradually attracted attention in recent years. Vorinostat combined with bortezomib in the treatment of multiple myeloma can prolong the median survival of patients. Enrollment was non-refractory multiple myeloma patients with ECOG score ≤2 who had progressed on previous treatment.

Vorinostat, an HDAC inhibitor, sensitizes breast cancer cells to taxanes and mAbs by inhibiting HDAC6 and Hsp90 pathological proteins.

Can Anticancer Drug Vorinostat Clear Latent HIV?

Researchers from the University of North Carolina at Chapel Hill published a groundbreaking research paper in the journal Nature on July 25, 2012, demonstrating that a deacetylase can be used to treat certain types of lymphoma. The enzyme inhibitor drug — vorinostat — clears out latent HIV in a patient’s body. The researchers conducted a series of experiments to evaluate the drug’s potential to activate and destroy latent HIV virus.

Initially, laboratory experiments measuring levels of active HIV virus in CD4+ T cells showed that vorinostat unmasked latent HIV virus in these cells. Next, eight HIV-infected men who remained medically stable on antiretroviral therapy were given vorinostat, and their levels of active HIV were tested and compared to levels before taking the drug. The researchers found an average 4.5-fold increase in HIV viral RNA levels in CD4+ T cells in these patients receiving vorinostat, confirming that the HIV virus was unmasked. This is the first published study to demonstrate the potential of sirtuin inhibitors to break latency in the latent viral reservoir. The study provides compelling evidence that a new strategy may be employed to directly attack and eradicate latent HIV infection. Breaking the latency of HIV virus is only the first step in curing HIV virus infection.

Reference

  1. Vorinostat – WikiPedia
  2. Advances in Pharmacology and Toxicology of Antineoplastic Drug Vorinostat

Vorinostat Suppliers and Manufacturers

As a vorinostat supplier and manufacturer with a strict standard product quality system certificate, Zhishang Chemical has long been providing the best vorinostat raw materials to customers all over the world.

Over the years, relying on professional team experience and customer-centric team concept to meet customer needs in a timely manner, our company enjoys a high reputation in the world. At present, our company has served more than 6,000 customers and has established long-term cooperative relations with customers from many countries.

If you have a demand for vorinostat and related products, please contact our service staff Zhishang Chemical – White directly, and we will provide you with high-quality products at the best price.

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