HIF1A

(redirected from HIF-1alpha)

HIF1A

A gene on chromosome 14q23.2 that encodes hypoxia-inducible factor-1 (HIF1), a transcription factor produced by mammalian cells cultured under reduced oxygen tension, which plays an essential role in homeostatic responses to hypoxia, activating the transcription of over 40 genes including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia.

HIF1 plays an essential role in embryonic vascularisation, tumour angiogenesis and pathophysiology of ischaemic disease. HIF1 is a heterodimer composed of an alpha subunit (encoded by HIF1A) and a beta subunit (aryl hydrocarbon receptor nuclear translocator) encoded by ARNT.

Molecular pathology
Overexpression of a natural antisense transcript (aHIF) of HIF1A is associated with nonpapillary renal carcinomas.
References in periodicals archive ?
The Company presented preclinical data on the HIF-1alpha antagonist at the 2008 AACR annual meeting in San Diego, California.
The other novel drug candidates in the company's pipeline include PX-478, an HIF-1alpha inhibitor, PX-866, a PI3-kinase inhibitor, and an early-stage thioredoxin reductase inhibitor.
Prior preclinical studies conducted by the Duke team demonstrated that inhibition of HIF-1alpha (hypoxia-inducible factor-1 alpha) caused near-complete destruction of tumor vessels and significantly improved radio-sensitivity in radiation resistant breast tumors.
HIF-1alpha is responsible for activating the production of new blood vessels when a tumor outgrows its blood supply.
The combination portion will determine if the addition of Panzem(R) NCD will restore tumor response by blocking tumor growth at both the level of the VEGF receptor and by inhibiting HIF-1alpha.
In this preclinical study, 2ME2 also showed a significant improvement in tissue oxygenation, which should result in improved responsiveness to therapy, and a decrease in HIF-1alpha (hypoxia inducible factor-1alpha).
Panzem(R) disrupts microtubule function and inhibits not only NFkappaB, but also the nuclear transcription factor, HIF-1alpha.
MKC-1 decreased the activity of several proteins that play a role in promoting tumor growth (GSK-3beta, pNFkappaB, pJAK2, pSTAT3, HIF-1alpha and pAkt).
Based on results from both preclinical experiments and mechanism-of-action studies, we believe that 2ME2 may be particularly well-suited for this patient population because these tumors are highly angiogenic and frequently harbor PTEN mutations, which result in high levels of HIF-1alpha protein.
Prior studies conducted by the Duke team demonstrated that the inhibition of HIF-1alpha causes near-complete destruction of tumor vessels and significantly improved radio-sensitivity in radiation resistant breast tumors.
ENMD-1198, a new chemical entity (NCE) derived from 2-methoxyestradiol (2ME2), was designed to decrease metabolism while retaining 2ME2's multiple mechanisms of action, including inducing apoptosis, disrupting microtubules, and inhibiting HIF-1alpha.
Nasdaq: ENZN) will be presenting Inhibition of HIF-1alpha antagonist from in vitro and in vivo studies on Sunday, April 13, at the 2008 American Association for Cancer Research (AACR) meeting in San Diego, California.