Drug Detail

Information about AUY922

Generic Name
Brand Name (US)
Drug Type
Approval Status
Phase 2
Overall Strategy
KIT Protein Based
Destroy KIT
Drug Category
HSP90 inhibitor

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.



LRG Story about the discovery of Hsp90 inhibitors for GIST.


Full text article - NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models - Jensen -2008


Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells


Full text article - NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis


AACR 2012 - HSP90 inhibitor NVP-AUY922 exhibits the potent antiproliferative effect in gastrointestinal cancer cells with a lack of PTEN expression

Trials of this drug


Phase I-II Study to Determine the Maximum Tolerated Dose (MTD) of AUY922 in Advanced Solid Malignancies, and Efficacy in HER2+ or ER+ Locally Advanced or Metastatic Breast Cancer Patients.


Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor


A Study of AUY922 for GIST(Gastrointestinal Stromal Tumor) Patients

Trial results

  ASCO 2009 phase I, A phase I dose escalation study of AUY922, a novel HSP90 inhibitor, in patients with advanced solid malignancies
  ASCO 2009 - Pharmacodynamics and pharmacokinetics of AUY922 in a phase I study of solid tumor patients.
  ASCO 2010 - AUY922, a novel HSP90 inhibitor: Final results of a first-in-human study in patients with advanced solid malignancies.

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