Your Ultimate Guide to SR9009

SR 9009 and Its Research Purposes 

SR9009 has powerful effects in research. It is a synthetic compound, specifically activates REV-ERBs, which are crucial elements of the body’s circadian clock system. 

Circadian rhythms have a significant influence on cell growth and metabolism, and they can also affect the advancement of specific diseases, particularly cancer. Adjusting this circadian mechanism through medication could potentially serve as an effective method for cancer treatment. 

SR 9009 Triggers REV-ERB Based Small Cell Lung Cancer Inhibition

In this study, the researchers tested the effectiveness of SR 9009, a compound that activates REV-ERB, in treating small cell lung cancer (SCLC) in a controlled laboratory setting. 

They used both chemosensitive cells (H69 and H446, which respond well to chemotherapy) and chemoresistant cells (H69AR and H446DDP, which are resistant to chemotherapy) to evaluate SR9009’s efficacy. 

The anti-cancer effect of SR 9009 was then further confirmed using subcutaneous tumor models of SCLC, which involves injecting cancer cells under the skin to create a solid tumor for experimental purposes. 

Researchers investigated the connection between REV-ERBα and the anti-SCLC impact of SR 9009. They carried out Chromatin immunoprecipitation (ChIP) sequencing tests to pinpoint potential DNA sequences directly controlled by REV-ERBα.  

The regulation of autophagy by REV-ERBα and its potential mechanism in the context of SR9009-based SCLC treatment were scrutinized. 

Researchers established SR 9009 is uniquely toxic to both chemosensitive and chemoresistant SCLC cells. The REV-ERBα protein played a critical role in SR9009’s antitumor effects on SCLC. 

They discovered that the primary autophagy gene, which is vital in autophagy – a cellular process that degrades and recycles unneeded or malfunctioning cell components, was directly targeted by REV-ERBα. This gene was suppressed within Small Cell Lung Cancer (SCLC) by SR 9009, an activator of REV-ERB..

Moreover, the interaction between REV-ERBα and the autophagy gene, Atg5, hindered the activity of autophagy, which led to the cytotoxic (cell-killing) effects of SR 9009 in SCLC cells.

In conclusion, research indicates that SR 9009, a REV-ERB agonist, has shown promising capability as a strategy in the reception of small-cell lung cancer (SCLC). This is achieved through the suppression of the core autophagy gene Atg5.

The studies also suggest that SR 9009 may have an anti-SCLC effect by inhibiting autophagy. Furthermore, the autophagy-related gene 5 (Atg5) appears to be a direct target of REV-ERBα and is suppressed following treatment with SR 9009. 

This suggests that SR 9009 could play a significant role in autophagic signaling. The data also indicates that SR 9009 might cause abnormalities in autophagy by repressing the Atg5 gene, resulting in an anti-SCLC effect. Therefore, the REV-Erb agonist SR9009 could potentially offer a new approach to cancer.  

SR 9009 Heart function 

The fundamental timekeeping component, REV-ERB, is crucial for the functioning of the heart. Past research has demonstrated that the REV-ERB agonist SR 9009 can improve heart restructuring in models subjected to pressure overload, specifically with transverse aortic constriction (experimental model in mice to simulate conditions of pressure overload-induced cardiac hypertrophy and heart failure).

Nevertheless, it was uncertain whether SR 9009 actually operates via cardiac REV-ERB, considering that SR 9009 may affect other proteins. REV-ERB present in non-cardiac tissues could indirectly control cardiac functions.

To investigate this issue, researchers created a cardiac-specific double knockout mouse model for REV-ERBα/β (referred to as cDKO).

Findings in this study of SR 9009 revealed that a deficiency of REV-ERB in the heart results in significantly dilated cardiomyopathy following Transverse Aortic Constriction (TAC).

This was observed to be more severe when compared to the wild-type (WT) control mice. These results affirm the pivotal role of REV-ERB in safeguarding the heart against the strain caused by pressure overload.

Even in the case of cDKO mice, the cardioprotective properties of SR 9009 against Transverse Aortic Constriction (TAC) are maintained. Furthermore, whether SR 9009 was administered at the peak or trough of REV-ERB expression, it demonstrated comparable cardioprotective effects.

This hints at the possibility of REV-ERB-independent mechanisms playing a significant role in the cardioprotection offered by SR 9009 following TAC.

Finally, the research emphasizes that when REV-ERB is genetically removed from cardiomyocytes, the adverse remodeling of the heart in response to pressure overload is expedited.

Additionally, scientists discovered that SR 9009 provides a cardioprotective effect against pressure overload, even in the absence of REV-ERB, suggesting that this protection isn’t solely dependent on REV-ERB.

SR 9009 Lung Injury in Sepsis 

Rev-Erbα functions as a nuclear heme receptor and a transcriptional repressor. It’s a crucial element for the molecular clock that regulates daily metabolic rhythms. However, its specific roles in acute lung injury (ALI) were still not clearly understood or defined.

Therefore, this study on SR 9009 focuses on investigating the impact of Rev-Erbα on lung damage in mice with sepsis.

A sepsis model in mice is created by administering an injection of lipopolysaccharide (LPS). Following this, the expression levels of various proinflammatory cytokines are examined.

These include tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10). The testing for these cytokines occurs in both RAW246.7 cells, a type of macrophage cell line, and lung tissues.

In mice with sepsis constructed through LPS, the inflammatory response is noticeably heightened. However, the administration of SR 9009 seemed to alleviate this response.

Additional experiments conducted on cells reveal that activating Rev-Erbα pharmacologically through SR 9009 can lessen the inflammatory response induced by LPS. This reduction is achieved by suppressing the activation of NF-κB, which is regulated by TLR4.

Sepsis triggers an increase in the W/D ratio and elevates the levels of malondialdehyde (MDA), lactic acid (LA), and superoxide dismutase (SOD). Simultaneously, it suppresses the levels of glutathione (GSH). However, treatment with SR9009 has been observed to effectively counter these effects, resulting in beneficial impacts on metabolism.

Furthermore, the administration of SR 9009 combats conditions of acidosis and hypoxemia. It does this by effectively reducing arterial PaCO2 levels and enhancing arterial PaO2, SO2, HCO3-, lactic acid concentration, and blood pH levels.

The results obtained affirm that administering SR 9009 treatment can mitigate lung injury caused by sepsis. Furthermore, these findings suggest that targeting Rev-Erbα could potentially be a valuable strategy in both preventing and managing Acute Lung Injury (ALI).

Relationship Between SR 9009 and Its Effects on Cells 

The nuclear receptors, REV-ERBα and -β, create a connection between circadian rhythms and metabolism. 

Similar to other nuclear receptors, the activity of REV-ERB can be managed by ligands, which include naturally occurring heme.

Cell Growth and Metabolism, Independent of REV-ERB

It has been reported that a potential ligand, SR 9009, can produce a variety of positive effects, not only in healthy animal models and cell systems but also in those that are diseased.

Nonetheless, the direct role of REV-ERBs in these beneficial effects brought about by SR 9009 hasn’t been fully explored. This is because the experiments conducted did not completely exclude both proteins from the process.

In this report, researchers presented the creation of a mouse model that allows for the conditional genetic deletion of REV-ERBα and -β. 

The findings demonstrate that SR 9009 has the ability to reduce cell viability, restructure cellular metabolism, and modify gene transcription in hepatocytes and embryonic stem cells that lack both REV-ERBα and -β.

Consequently, it is clear that SR 9009 should not be solely associated as a substitute for REV-ERB activity. This suggests that SR9009 may have other mechanisms of action or affect other pathways in addition to its interaction with REV-ER .

Therefore, it’s not accurate to consider SR 9009 just as a stand-in for REV-ERB activity. 

The Growth and Development of Specific Types of Brain Cells

In this study, investigators utilized SR 9009, a synthetic REV-ERB stimulant known to reduce anxiety in mice. It’s used as a treatment on both undifferentiated and neuronally differentiated cultured rat adult hippocampal neural stem/progenitor cells (AHPs).

The research observed an increase in the expression of Rev-erbβ during the process of neurogenesis in cultured rat adult hippocampal neural stem/progenitor cells (AHPs). Further analysis, involving the knockdown of Rev-erbβ, suggested that REV-ERBβ plays a regulatory role in the proliferation and neurite outgrowth of these cultured rat AHPs. 

When the REV-ERB agonist SR 9009 was administered at a minor concentration (0.1 µM), it was observed to stimulate the extension of neurites, a crucial part of neurogenesis, in cultured rat adult hippocampal neural stem/progenitor cells (AHPs). Conversely, the introduction of a larger quantity of SR9009 (2.5 µM) led to a decrease in neurite outgrowth within these same cells. 

In-depth analysis of the regulatory mechanism of SR 9009 revealed that it has an impact on the expressions of downstream target genes of REV-ERBβ, specifically Ccna2 and Sez6 (protein coding genes). The study found that these genes were subject to modulation by SR 9009.

The findings revealed that SR 9009, a synthetic REV-ERB agonist, modulates the activity of REV-ERBβ in these cells. It was observed that this modulation occurs in a concentration-dependent manner.

This also indicated that SR 9009 influences the proliferation and neurite outgrowth/suppression of these cells. Furthermore, it was found that certain genes, including Ccna2 and Sez6, were affected by SR 9009. These insights suggest potential therapeutic applications for conditions like bladder cancer where the clock gene NR1D1, which is related to REV-ERBβ, might be a novel target.

SR 9009 v.s GW501516

As delineated previously, SR9009 showed cardio-protective attributes. GW501516, also known as Cardarine, is also often referred to as a selective androgen receptor modulator. While GW501516 is actually a PPAR agonist and has also presented cardiovascular effects when tested amongst subjects. Here the evidence will be analyzed and compared. 

SR 9009 

For these research purposes, investigators created a strain of mice with the REV-ERBα/β genes specifically removed from their heart cells. These mice are referred to as cardiac-specific double knockout mice (cDKO).

The research findings emphasize that the removal of REV-ERB, a gene in heart muscle cells known as cardiomyocytes, speeds up harmful changes to the heart’s structure when it is subjected to pressure overload. These findings showed that SR 9009, a compound used in the study, can protect the heart against pressure overload independently of its interaction with REV-ERB .

GW501516

When used at small concentrations, GW501516 acts as a selective ligand for PPARδ, a type of protein receptor.

For research purposes, studies have shown that when combined with exercise training, Cardarine significantly increases endurance in mice., GW501516 increased the quantity of oxidative myofibers, resulting in a 70% increase in the distance and duration that mice can run. This is achieved through the transcriptional activation of PPARδ. 

Although each compound affects the cardiovascular system. SR 9009 exhibits cardio-protectiveness, while GW501516 seems to show increased exercise capacity in test subjects. 

SR 9009 and DSIP 

To reiterate our description above about the circadian rhythm is our body’s internal clock that regulates numerous functions over a 24-hour cycle,This includes: sleep, eating habits, hormone release, and body temperature changes. SR 9009 and DSIP (Delta sleep-inducing peptide) both influence the circadian clock in several ways. 

SR 9009, often referred to as a synthetic REV-ERB agonist, influences the circadian rhythm by interacting with nuclear receptors REV-ERBα and REV-ERBβ. These receptors play a critical role in maintaining the body’s internal biological clock. By binding to these receptors, SR 9009 can influence various biological processes that operate on a 24-hour cycle.

This includes altering the expression of core-clock genes in the hypothalamus and metabolic genes in skeletal muscle.

Skeletal muscle, also known as voluntary muscle, is a type of striated muscle tissue that is attached to bones, that enables body movement through its contraction and relaxation under conscious control. This also indicates the ability to act on the muscle cells.

This expression of core-clock genes led to changes in sleep patterns, energy expenditure, and overall metabolism. It’s also been found to have effects independent of the functional circadian clock, such as inhibiting certain immune responses.

Furthermore, SR 9009 has been shown to impact cell viability and alter gene transcription, potentially influencing the functioning of different cell types in test subjects.

Although not a selective androgen receptor modulator, Delta Sleep-Inducing Peptide (DSIP), a neuropeptide involved in sleep regulation, interacts with the circadian rhythm in several ways. It influences physiological processes like temperature, blood pressure, and heart rate in rats, which are regulated by the circadian rhythm.

DSIP also impacts the transition from wakefulness to sleep and affects levels of prolactin and the activity of N-Acetyl Transferase, both key elements in circadian rhythm regulation. Correlations have also been found between DSIP plasma concentrations and the human circadian rhythm.

SR 9009 and DSIP both interact with the circadian rhythm but in distinct ways. SR 9009, a synthetic REV-ERB agonist, influences the circadian rhythm by binding to nuclear receptors REV-ERBα and REV-ERBβ, impacting various biological processes like sleep patterns, energy expenditure, and metabolism. It also affects cell viability and gene transcription.

On the other hand, DSIP, a neuropeptide involved in sleep regulation, affects the circadian rhythm by influencing physiological processes such as temperature, blood pressure, and heart rate, and by affecting the transition from wakefulness to sleep. It also impacts levels of prolactin and the activity of N-Acetyl Transferase, key elements in circadian rhythm regulation.

The legality of SR9009 Stenabolic

SR9009 Stenabolic is for research use only. It is not approved by the World Anti-Doping Agency and is listed as a research chemical by the FDW. SR90009 Stenabolic is for laboratory use and is predominantly used in animal studies and the clinical setting. Continue reading to learn about these Stenabolic scientific studies in greater detail.