Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Journal Article
PMID (22295124)
Authors Carew JS, Esquivel JA, Espitia CM, Schultes CM, Mülbaier M, Lewis JD, Janssen B, Giles FJ, Nawrocki ST
Title ELR510444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcinoma.
Journal Vol Issue Date Pages Journal Short Title
PloS one 7 1 2012 e31120 PLoS One
URL
Abstract Text Hypoxia-inducible factor (HIF) is an attractive therapeutic target for renal cell carcinoma (RCC) as its high expression due to the loss of von Hippel-Lindau (VHL) promotes RCC progression. Considering this, we hypothesized that ELR510444, a novel orally available small molecule inhibitor of HIF activity, would reduce angiogenesis and possess significant activity in RCC. The mechanism of action and therapeutic efficacy of ELR510444 were investigated in in vitro and in vivo models of RCC.ELR510444 decreased HIF-1α and HIF-2α levels, reduced RCC cell viability and clonogenic survival, and induced apoptosis. VHL-deficient RCC cells were more sensitive to ELR510444-mediated apoptosis and restoration of VHL promoted drug resistance. Higher concentrations of ELR51044 promoted apoptosis independently of VHL status, possibly due to the microtubule destabilizing properties of this agent. ELR510444 significantly reduced tumor burden in the 786-O and A498 RCC xenograft models. These effects were associated with increased necrosis and apoptosis and inhibition of angiogenesis.ELR510444 is a promising new HIF inhibitor that reduced RCC cell viability, induced apoptosis, and diminished tumor burden in RCC xenograft models. ELR510444 also destabilized microtubules suggesting that it possesses vascular disrupting and anti-angiogenic properties. Further investigation of ELR510444 for the therapy of RCC is warranted.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
ELR510444 ELR510444 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
ELR510444 ELR-510444 ELR510444 is a small molecule inhibitor of HIF, which may result in apoptosis and has the potential to disrupt the tumor vasculature environment (PMID: 22295124).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
VHL loss renal cell carcinoma sensitive ELR510444 Preclinical - Cell line xenograft Actionable In a preclinical study, renal cell carcinoma cells deficient for VHL were sensitive to ELR510444 both in culture and in cell line xenograft models (PMID: 22295124). 22295124