Panobinostat is an experimental drug developed by Novartis

Novartis

Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...

 for the treatment of various cancers. It is a hydroxamic acid

Hydroxamic acid

A hydroxamic acid is a class of chemical compounds sharing the same functional group in which an hydroxylamine is inserted into a carboxylic acid. Its general structure is R-CO-NH-OH, with an R as an organic residue, a CO as a carbonyl group, and a hydroxylamine as NH2-OH. They are used as metal...

 and acts as a non-selective HDAC inhibitor.

Clinical trials

, it is being tested against cutaneous T cell lymphoma

Cutaneous T Cell lymphoma

Cutaneous T cell lymphoma is a class of non-Hodgkin's lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin's lymphomas , CTCL is caused by a mutation of T cells. The malignant T cells in the body initially migrate to the skin, causing various lesions to appear...

 (CTCL), chronic myelogenous leukemia

Chronic myelogenous leukemia

Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood...

, myelodysplastic syndromes, breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, prostate cancer

Prostate cancer

Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

 and other types of malignant disease in a number of Phase II and III clinical trial

Clinical trial

Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s,
for example a Phase III study for CTCL.

Preclinical studies

Panobinostat has been found to synergistically act with sirolimus

Sirolimus

Sirolimus , also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. A macrolide, sirolimus was first discovered as a product of the bacterium Streptomyces hygroscopicus in a soil sample from Easter...

 to kill pancreatic cancer cells in the laboratory in a Mayo Clinic

Mayo Clinic

Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...

 study. In the study, investigators found that this combination destroyed up to 65 percent of cultured pancreatic tumor cells. The finding is significant because the three cell lines studies were all resistant to the effects of chemotherapy – as are many pancreatic tumors.

Panobinostat has also recently been found to significantly increase in vitro

In vitro

In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

the survival of motor neuron

Survival of motor neuron

The Survival of Motor Neuron is a protein involved in the assembly of snRNPs, the essential components of spliceosomal machinery. A lack of SMN due to SMN1 deletion results in widespread splicing defects, especially in spinal motor neurons, and is one cause of spinal muscular atrophy.SMN also...

 (SMN) protein levels in cells of patients suffering from spinal muscular atrophy

Spinal muscular atrophy

Spinal Muscular Atrophy is a neuromuscular disease characterized by degeneration of motor neurons, resulting in progressive muscular atrophy and weakness. The clinical spectrum of SMA ranges from early infant death to normal adult life with only mild weakness...

.

Mechanism of action

Panobinostat inhibits multiple histone deacetylase

Histone deacetylase

Histone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone...

 enzymes, a mechanism leading to apoptosis

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

of malignant cells via multiple pathways.