Drug Detail

Information about HSP990

Generic Name
IND	HSP990
Brand Name (US)
Manufacturer	Novartis/Vernalis
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Phase 1
Indications
Overall Strategy	KIT Protein Based
Strategy	Destroy KIT
Drug Category	HSP90 inhibitor

HSP990 is an oral Hsp90 inhibitor being developed by Novartis in a collaboration with Vernalis. It is also known by NVP-HSP990.
Drug Class: HSP90 inhibitors
Heat Shock Protein 90 (Hsp90) is a protein that has several functions in cells. It is an emerging therapeutic target of interest for the treatment of cancer. Proteins are the mainstay of structural and signaling elements of all cells. Hsp90 is a molecule that maintains the conformation and activity of specific proteins in the cell, also called "client proteins" of Hsp90. KIT is one of the client proteins of Hsp90. Hsp90 enables cancer cell survival by maintaining the function of their mutated client proteins including the KIT and PDGFRA proteins in GIST. Inhibition of Hsp90 therefore has the potential to destroy the activated KIT/PDGFRA proteins resulting in a therapeutic effect in GIST. Since the target of these drugs are Hsp90 and not KIT or PDGFRA, they should be unaffected by the secondary mutations that commonly cause resistance to Gleevec. In fact, preliminary work has suggested that the stronger KIT is activated, the better they work.
Drugs in this class include both oral and intravenous drugs. Some of the intravenous drugs, such as IPI-504, are also being developed as an oral version.
A derivative of 4,5-diarylisoxazole and a third-generation heat shock protein 90 (Hsp90) inhibitor with potential antineoplastic activity. Hsp90 inhibitor AUY922 has been shown to bind with high affinity to and inhibit Hsp90, resulting in the proteasomal degradation of oncogenic client proteins; the inhibition of cell proliferation; and the elevation of heat shock protein 72 (Hsp72) in a wide range of human tumor cell lines. Hsp90, a 90 kDa molecular chaperone, plays a key role in the conformational maturation, stability and function of other substrate or "client" proteins within the cell, many of which are involved in signal transduction, cell cycle regulation and apoptosis, including kinases, transcription factors and hormone receptors. Hsp72 exhibits anti-apoptotic functions; its up-regulation may be used as a surrogate marker for Hsp90 inhibition.