CANTEX-Cell-Membrane
Why-RAGE-is-important
overactivation of rage

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RAGE is a cell receptor that is normally activated by several kinds of molecules, including advanced glycation endproducts (AGEs)

 

When it is overstimulated, RAGE is believed to worsen multiple types of cancers and inflammatory diseases, including:

  • Pancreatic cancer and related pain
  • Bone pain related to cancer spread
  • Brain toxicity due to chemotherapy
  • Inflamed lungs due to COVID-19 infection
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rage-overactivation-cancer
Rage overactivation in cancer

Overactivation of the RAGE receptor stimulates cell signaling pathways that help tumors to grow and spread (metastasize)

RAGE ligands include the HMGB1 and S100 proteins

 

Expressed and secreted by cancer cells

 

Associated with increased metastasis and poorer outcomes in a wide variety of tumors

 

Ligand binding and activation of RAGE activates intracellular signaling pathways that stimulate proliferation, invasion, chemotherapy resistance, and metastasis

 

 

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rage overactivation bone pain
rage overactivation in bone pain

Metastatic tumors in bone produce HMGB1 which overactivates RAGE and stimulates pain nerves

Pain nerves send signals through the spinal cord to the brain where it is experienced as bone pain

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What is chemo brain?

Chemotherapy can cause toxic side effects in the brain that impair attention, memory, learning, concentration, reasoning, processing speed, executive functions, and visuospatial skills

Chemotherapy-induced Cognitive Impairment (CICI), also known as chemo brain, occurs in up to 75% of patients during chemotherapy

Chemo brain persists after treatment in up to 35% of patients

CICI is common in breast cancer and no medications are available for either prevention or treatment

In animal models of chemo brain, inhibition of RAGE prevented cognitive impairment

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How AZELIRAGON WORKS
AZELIRAGON

Azeliragon is an investigational once-a-day oral drug that blocks RAGE which may reduce cancer growth, metastatic bone pain, chemo brain, and the severity of COVID-19 infection

AZELIRAGON

 

 

 

Azeliragon is a RAGE inhibitor that blocks attachment of the full spectrum of RAGE ligands

 


 

Oral once-daily administration

 


 

Safety confirmed in clinical trials involving 2,237 patients primarily with Alzheimer’s Disease

 

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RAGE overactivation in COVID-19
RAGE overactivation in COVID-19

Overactivation of the RAGE receptors in the lung can increase inflammation and injury and worsen the severity of the COVID-19 infection

Clinical and preclinical studies have demonstrated that increased RAGE signaling occurs in patients with moderate or severe COVID-19 infection. The mechanisms underlying this include increased inflammation, endothelial injury, and thrombosis.

 

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