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AUY922
Phase 1, N/A, Phase 2
HSP90 inhibitor
Hemat
AUY922 is a non-geldanamycin derivative Hsp90 inhibitor. Areas of Research: Breast cancer, non–small cell lung cancer (NSCLC), and other solid tumors.

Compound DescriptionNon-geldanamycin derivative Hsp90 inhibitor

Areas of ResearchBreast cancer, non–small cell lung cancer (NSCLC), and other solid tumors

Proposed Mechanism of ActionHsp90 is a ubiquitously expressed chaperone protein which is a critical regulator of the proper folding and conformation of many oncogenic client proteins, including human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), epidermal growth factor receptor (EGFR), AKT, c-KIT, B-Raf, and enchinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK).1,2 AUY922 inhibits the Hsp90 protein complex.1,2 This results in potential degradation of client proteins involved in oncogenesis, pro-survival signaling, and anti-apoptosis.1,2

Key Preclinical DataIn in vivo and in vitro preclinical studies, AUY922 binds to Hsp90 with high affinity in cancer cell lines of different tumor types. It destabilizes Hsp90 chaperoning complex and induces degradation of Hsp90 client proteins. This then results in induction of Hsp70, a sensitive pharmacodynamic marker of Hsp90 complex disruption.3,4

Clinical StatusThe first-in-human phase I/II dose escalation study evaluating AUY922 is complete, and the maximum tolerated dose (MTD) was determined.1 Four phase II studies are ongoing to determine the clinical benefits of AUY922 in patients with NSCLC. One of these studies is evaluating the efficacy of AUY922 compared to that of pemetrexed or docetaxel in patients with EGFR mutations who have progressed on prior EGFR TKI treatment.5 Other ongoing NSCLC studies are exploring AUY922 in patients who have received at least two lines of chemotherapy,6 in patients with "acquired resistance" to EGFR TKIs,7 and in patients with ALK-rearranged advanced NSCLC who have acquired resistance to prior ALK TKI therapy.8

MOA data is based on in vitro/in vivo data. Clinical benefit is unknown.
AUY922 is an investigational compound. Efficacy and safety have not been established.
There is no guarantee that AUY922 will become commercially available.
References
  1. Samuel TA, Sessa C, Britten C, et al. AUY922, a novel HSP90 inhibitor: final results of a first-in-man study in patients with advanced solid malignancies. Poster presented at: 46th Annual Meeting of the American Society of Clinical Oncology (ASCO); June 4–8, 2010; Chicago, IL.
  2. Jensen MR, Schoepfer J, Radimerski T, et al. NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models. Breast CA Res. 2008;10(2):1–12.
  3. Eccles SA, Massey A, Raynaud FI, et al. NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Res. 2008;68(8)2850–2860.
  4. Novartis, data on file, 2014.
  5. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01646125. Updated September 16, 2013. Accessed January 10, 2014.
  6. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01124864. Updated May 16, 2013. Accessed January 10, 2014.
  7. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01259089. Updated May 7, 2013. Accessed January 10, 2014.
  8. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01752400. Updated April 1, 2013. Accessed January 10, 2014.
  9. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01484860. Updated June 7, 2012. Accessed January 10, 2014.
  10. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01668173. Updated October 14, 2013. Accessed January 10, 2014.
  11. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01485536. Updated January 15, 2014. Accessed January 16, 2014.
  12. National Institutes of Health (NIH). ClinicalTrials.gov. www.clinicaltrials.gov/ct2/show/NCT01404650. Updated August 14, 2013. Accessed January 10, 2014.

The information contained herein was last updated on April 12, 2013.

All Compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.

The search results, details, and descriptions of clinical trials viewed in this app are supplied by ClinicalTrials.gov and EUtrialregistry.com. This information is maintained by a third party over whom Novartis Pharmaceuticals Corporation has no control. As such, Novartis Pharmaceuticals Corporation does not guarantee the accuracy, completeness, adequacy, or any other aspect of the information contained on this site.