SR9009, also known as Stenabolic, is a synthetic drug designed to manipulate our natural circadian rhythms. Our bodies function in a coordinated manner, in 24-hour cycles that are adjusted to the rise and fall of the sun. This pattern is called the circadian rhythm.
The circadian rhythm is maintained through a loop mechanism that turns genes on and off (when CLOCK and BMAL1 genes are turned on, they turn on PER and CRY. Then, PER/CRY turn BMAL1/CLOCK off and the 24-hour cycle resets).
The REV-ERBs are a pair of proteins that stabilize our internal clock by turning BMAL1 off. They are, in turn, activated by the heme group. Heme is a small iron-containing compound found all throughout our body, for example, in red blood cells. You may notice more intense pumps during training sessions for this reason.
SR9009 is a compound that enhances REV-ERB activity (known as agonists) and has good bioavailability if it is prepared for sublingual administration (delivered under the tongue). It is documented that it is not orally-bioavailable (processed in the gut/liver). For this reason the product is produced as a liquid, rather than a capsule.
Mechanism of Action
All the effects observed for SR9009 derive from REV-ERB (NR1D1, NR1D2) activation in the body.
Besides its effect on the circadian rhythm (suppression of BMAL1 production), REV-ERB affects many other functions related to energy production.
REV-ERB is mainly found in liver, muscle, and fat tissue:
- Liver: REV-ERB affects the rhythm of 90% of the about 900 genes under circadian control in the liver. It turns off the genes that produce glucose without altering insulin sensitivity.
- It also turns off genes that generate new fat cells and reduces the inflammatory response (by affecting macrophage production).
- Muscles: REV-ERB promotes the burning of fat, increases the activity of mitochondria, and promotes the generation of new while decreasing the destruction of old mitochondria
- Fat cells: REV-ERB turns off the genes responsible for storing fat and decreases triglyceride production
1) Weight Loss
Mice injected with SR9009 for 7 days lost weight due to a decrease in fat mass. Food intake was not affected.
Similarly, diet-induced obese mice injected with SR9009 for 30 days lost 60% more weight than control animals. Blood levels of triglycerides, total cholesterol, free fatty acids, and insulin levels also decreased.
In genetically obese mice, SR9009 stopped weight gain after 12 days without affecting glucose levels or insulin tolerance.
2) Blood Cholesterol
SR9009 given for 7 to 10 days reduced blood levels of triglycerides and total cholesterol in mice.
Genetically modified mice undergoing a high cholesterol diet to obtain a fat profile similar to humans were given SR9009 for 8 weeks. Total cholesterol and triglycerides were similarly lowered, while LDL cholesterol was lowered but HDL cholesterol was unaffected.
Mice treated with SR9009 for 30 days showed increased endurance. They ran for a longer time and covered more distance than controls.
SR9009 increased the number of total and active mitochondria in muscle cells (by repressing autophagy genes).
4) Decreasing Inflammation
SR9009 diminished lung inflammation in rats (by reducing the production of TNF-alpha).
It also reduced the production of inflammatory molecules (CCL2, MMP-9) in rat nerve cells.
5) Heart Disease
Genetically modified mice susceptible to hardening of the arteries were treated with SR9009 for 7 weeks. The size of the blood vessel lesions was reduced, while food intake, body weight, and blood fat levels were not affected.
In both normal and genetically modified old mice, SR9009 injected for 28 days improved heart function.
In mice with surgically induced heart growth (hypertrophy), SR9009 given for 2 weeks reduced heart size and weight, with no effect on blood pressure.
As an activator of REV-ERB, S9009 changes sleep/wake patterns in mice. However, its effects are short-term and last only 12 hours.
Mice injected with SR9009 during daytime (this is when the mice are supposed to be asleep) were more active during the day and had less deep sleep (less REM and slow-wave sleep). However, when SR9009 was injected during the night (when mice are active), it had no effect.
SR9009 may potentially help in maintaining wakefulness when the drive for sleep is significant including shift work, jet lag, and some sleep-related disorders.
SR9009 injected twice a day for 3 to 10 days, decreased anxiety-like behavior in mice and was as effective as a benzodiazepine.
8) Tissue Damage (Fibrosis)
SR9009 decreased tissue damage in mice with induced liver scarring when treated with SR9009 for 2 weeks.