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SR9009 Anti-Cancer REV-ERB Agonist?

Discussion in 'Educating Doctors' started by DrEttinger, May 21, 2019.

  1. DrEttinger

    DrEttinger Choice, the only thing we control

    Hot off the presses. Until yesterday the research community believed a research chemical, that can be bought readily off the internet as a performance-enhancing neutraceutical, worked as a REV-ERB agonist, positively affecting aspects of our circadian rhythm. By doing so, "it raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combatting cancer." Pharmacological activation of REV-ERBs is lethal in cancer and oncogene induced senescence [1] (Jan 2018).

    In a Medical X Press release yesterday Circadian mechanism may not be driver behind compound linked to obesity and diabetes the study's senior author Mitchell Lazar, MD, Ph.D., director of the Institute of Diabetes, Obesity and Metabolism, said, "These findings have important implications because some of the previous studies concluded it was the circadian clock that was affecting metabolism or cell growth, through these compounds and producing the benefits related to diabetes, obesity, and cancer. That needs to be reconsidered, as our study shows these compounds work on something other than this clock factor." (May 2019)

    Even with the new data that another mechanism may be at work. SR9009 did show to have a beneficial effect on a number of cancer cell lines, including glioblastoma (brain cancer).

    "The regulation of autophagy and de novo lipogenesis by SR9009 and SR9011 plays a critical role in evoking an apoptotic response in malignant cells. Importantly, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth in vivo and improve survival without causing any overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective novel antitumor strategy, identifying the existence of a previously unknown class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are novel autophagy and de novo lipogenesis inhibitors with selective activity towards malignant and benign neoplasms." [1]

    Note: I have used many SARMS and SARM like compounds. I have used SR9009 to help cut body fat while maintaining my same workout and diet. It does work. I'm not condoning its use. I'm just commenting on its positive effects of creating improved lean muscle mass.
     
    Last edited: May 21, 2019
    LisaLearning likes this.
  2. Jack Kruse

    Jack Kruse Administrator

    SR9009, also known as Stenabolic, is a research drug that was developed by professor Thomas Burris of the Scripps Research Institute as an agonist of Rev-ErbA (i.e., increases the constitutive repression of genes regulated by Rev-ErbA)with a half-maximum inhibitory concentration (IC50) = 670 nM for Rev-ErbAα and IC50 = 800 nM for Rev-ErbAβ.

    Activation of Rev-ErbA-α by SR9009 in mice increases exercise capacity by increasing mitochondria counts in skeletal muscle.

    What few realize: Diabetics have a dawn phenomenon related to a lack of circadian cycling. A lack of light cannot be fixed by adding a drug. For prediabetes and Type-2 diabetes who regularly monitor their blood sugar, there is a well-known issue called the dawn phenomenon. It is characterized by a rise in blood sugar during the early morning hours, despite lifestyle measures and even medication. Sunlight has massive impacts on many circadian genes that alter mitochondrial biology. Most mitochondria in humans are in the brain, so the effect of sunlight on these genes should pay off handsomely to clinicians who understand the link. The Rev-erb gene is the gene that the electromagnetic force operates on.

    A lack of AM sunlight = a lack of electromagnetic force to activate the Rev-erb gene. An altered daily rhythm of expression of the Rev-erb gene underlies the dawn phenomenon. Future investigations to reverse diabetes must be built around light and not drugs to get a full understanding of the disease. Rev-erb is expressed only during the day but not at night. In humans, the rev-erb gene is found in GABA neurons and the gene’s expression is highly enriched in a particular brain area called the suprachiasmatic nucleus. The SCN is mainly composed of GABA neurons. Humans have a photopic retina because they are diurnal. When the body awakes and takes in food, insulin is secreted from the pancreas to signal the body to lower blood sugar. Insulin is more effective in doing this job upon waking than at other times of the day. This high insulin sensitivity is probably because the body is anticipating feeding behaviors upon waking up. Sunlight alters the daily functioning of the rev-erb gene in the brain to control insulin release and action in the gut. Neural Rev-erb must be operational to regulate mitochondria in the liver to control the hepatic insulin sensitivity rhythm. This quantum controller operates independently of eating behaviors or basal hepatic glucose production. In humans, we now know the Rev-erb gene in white blood cells, correlates well with the central clock function in the brain.

    The nuclear receptors REV-ERB (consisting of REV-ERBα and REV-ERBβ) and retinoic acid receptor-related orphan receptors (RORs; consisting of RORα, RORβ and RORγ) are involved in many physiological processes, including regulation of metabolism, development and immunity as well as the circadian rhythm. What does this imply? It means there is a specific part of the AM solar spectrum diabetics lack. Can you guess which one it is?

    [​IMG]

    Nuclear receptor Rev-erb α: is a heme receptor that coordinates circadian rhythm and metabolism.
     
    John Schumacher likes this.
  3. What is interesting to me is the spectrum of light our heme absorb during sunrise.
    Question - what is the emission spectrum from heme within our brain, specifically our Pituitary Gland?
     

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