HDAC Inhibitors

Histone Deacetylase Inhibitor Program

The human genome CloseGenome

All of the information encoded in the DNA of an organism.

consists of a complex collection of genes that are turned on or off depending on the needs of the cell at any given moment. Cancer occurs when gene expression CloseGene expression

The process by which genetic information encoded in the DNA is made useful for cell functions.

patterns change (genes inappropriately turned on or off) within cells. Tumors modify gene expression as a survival mechanism and for many other reasons, For example, turning off particular genes may enable a tumor CloseTumorAn abnormal growth of cells that may be the result of cancer.to multiply, to avoid apoptosis, CloseApoptosis

Programmed cell death or suicide that results from interrupted cellular functions.

or to become resistant to chemotherapy. One way to turn genes on or off is via chemical modifications on histone proteins. Histone proteins are structural components of chromosomes that essentially spool DNA, CloseDNA

An acronym for Deoxyribo Nucleic Acid, a genetic material encoding instructions for proteins and other necessary cellular components.

arranging and packing it  for storage within the nucleus of a cell.

Histone acetylation CloseAcetylation

A chemical reaction that adds a chemical group (acetyl) to a molecule.

alters the expression of genes important in cell cycle control, cell division, and apoptosis, by turning the genes on. Histone deacetylation CloseDeacetylation

A reaction that involves removing an acetyl group CloseAcetyl Group

A chemical group derived from acetic acid.

from a molecule.

does the opposite of histone acetylation by removing acetyl groups and turning the genes off. The process of histone deacetylation is performed by a group of enzymes called histone deacetylases (HDACs). Molecules or drugs that block HDACs (HDAC inhibitors) prevent HDACs from removing acetyl groups and this results in an increase in histone acetylation which increases the expression of certain genes. In this way, HDAC inhibitors effectively limit a tumor’s ability to multiply, to avoid apoptosis or to become resistant to chemotherapy. HDAC inhibitors have been shown to block cancer cell proliferation in vitro CloseIn vitro

An experiment performed outside of a living body, ie, in a petri dish, test tube, or culture.

and arrest cancer cell growth in vivo CloseIn vivoWithin the body of a human or animal.at non-toxic concentrations.

Market

There are broad potential applications of Pan-HDAC inhibitors for anti-cancer indications, including their use in combination with chemotherapy drugs and radiation in hematologic and solid cancers.

Specific HDAC enzymes play important roles in other physiological processes and there is growing interest to find uses for HDAC inhibitors in many disease areas including metabolic, neurological and immunological disorders as well as in treating bacterial and parasitic infections. For instance, in central nervous system (CNS) indications, HDAC inhibitors are active in models of epilepsy and migraine headaches, dementia, Alzheimer’s, Parkinson’s and Huntington’s disease (Kazantsev & Thompson, Nat Rev Drug Discov. 2008; Steffan JS et al. Nature. 2001). HDAC inhibitors are also active in inflammatory models including rheumatoid arthritis CloseRheumatoid arthritisAn auto-immune disease that causes the swelling and stiffening of the joints. (RA), juvenile RA, multiple sclerosis, CloseMultiple Sclerosis

An autoimmune condition that affects the ability of nerve cells in the brain and spinal cord to communicate with each other.

psoriasis, ClosePsoriasis

A common chronic, inflammatory disease that affects the skin and joints and is characterized by scaly patches on the skin.

lupus, CloseLupus

A chronic inflammatory disease that occurs when the body's immune system attacks its own tissues and organs.

sepsis, CloseSepsis

A condition that results from severe bacterial infection in the body. 

diabetes and hemorrhagic shock CloseHemorrhagic Shock

Trauma as a result of excess blood loss.

(Chipoy C. Drug Discovery Today. 2005; Gray SG, Dangond F. Epigenetics. 2006; Susick L, et al. J Cell Mol Med. 2009).  Finally, HDAC inhibitors have shown activity in antiviral, CloseAntiviral

A compound that prevents a virus' ability to multiply and spread.

antibacterial and antiparasitic CloseAntiparasitic

A compound used to treat diseases that are transmitted by parasites, including Lyme disease or trichinosis.

applications (Elaut G, et al. Curr Pharm Des. 2007).

Patents

Key patent protection in US and international territories will extend beyond 2024 with the possibility of patent term extensions during development.

Partnering

In April 2009, the company entered into a collaboration agreement with Servier pursuant to which Pharmacyclics granted to Servier an exclusive license for its Pan-HDAC inhibitors, including PCI-24781, for territories throughout the world excluding the United States. Under the terms of the agreement, Servier acquired the exclusive right to develop and commercialize the Pan-HDAC inhibitor product worldwide except for the United States and will pay a royalty to Pharmacyclics on sales outside of the United States. Pharmacyclics will continue to own all rights within the United States.