SR9009 is an experimental circadian rhytm modulator (RevErb-alpha agonist). In one hand, SR9009 is said to be attractive as a performance-enhancing agent, yet, in the other hand, its use has been discouraged because it is potentially harmful [1]. The desire to discourage its use has prompted development of its screening methods.
So far, SR9009 has revealed anti-inflammatory properties (suppressing activation of several pro-inflammatory cytokines including tumor necrosis factor alfa, whose downstream effect was suppression of tumor necrosis factor alpha) [2]. The anti-inflammatory effects have been shown in animal models of endometriosis, heart attack, Alzheimer’s disease and some autoimmune diseases [2,3,4,5]. In Alzheimer’s disease model mouse, SR9009 reversed cognitive deficits but it has been not shown whether it has nootropic properties (increasing cognitive performance in healthy animals or humans). Since SR9009 suppresses proinflammatory cytokines, it does not come as a surprise that it reduces neuroinflammation and neuropathic pain [6,7]. Furthermore, it reduces blood glucose levels that may be beneficial in the context of diabetes but not necessarily in healthy mic [8]. It has been shown that SR9009 interactions with antifungal and SSRI antidepressant drugs, and its metabolism varies between different cytochrome genotypes, warranting further caution interpreting dose-dependence of both desired and undesired effects [9]. The harmful effects of SR9009 is clearly more pronounced against cancer cells of mice when compared to normal cells (no overt toxicity) [10]; an effect suppressing the fat tissue was also shown. In a study investigating age-depended heart hypertrophy, SR9009 showed beneficial effects. Studies hint that SR9009 might be useful for treatment of sleep and anxiety diorders in rodents [11]. In humans, these properties have not been tested and there is a fundamental difference between mice and humans: mice are nocturnal animals while humans cannot be considered nocturnal. SR9009, like SR9011, increases energy expenditure, has antiatherogenic properties and may correct disrupted sleep patterns: this suggests that it is an interesting molecule for metabolic disease research. So far, no human studies have been performed and there is also a paucity of anecdotal reports of its effects; it is clearly a molecule in preclinical research phase. Moreover, safety cannot be assumed. The data concerning the relative safety of SR9009 in animals is not unequivocal. SR9009 is not a pure Rev-Erb-alpha agonist: in animals without the Rev-Erb proteins, SR9009 had harmful effects such as decreased cell viability, rewired cellular metabolism, and altered gene transcription in liver cells and embryonic stem cells, which indicate other mechanisms of actions as well as undesirable side effects [11]. Currently, it seems a quite promising rodent drug but the lack of clinical studies implies that the benefits for humans are quite speculative.
[1] https://www.ncbi.nlm.nih.gov/pubmed/27706103
[2] https://www.ncbi.nlm.nih.gov/pubmed/31411318
[3] https://www.ncbi.nlm.nih.gov/pubmed/29232411
[4] https://www.ncbi.nlm.nih.gov/pubmed/30973894
[5] https://www.ncbi.nlm.nih.gov/pubmed/30590045
[6] https://www.ncbi.nlm.nih.gov/pubmed/30792350
[7] https://www.ncbi.nlm.nih.gov/pubmed/30682503
[8] https://www.ncbi.nlm.nih.gov/pubmed/30639375
[9] https://www.ncbi.nlm.nih.gov/pubmed/30395700
[10] https://www.ncbi.nlm.nih.gov/pubmed/29320480
[11] https://www.ncbi.nlm.nih.gov/pubmed/25536025
[12] https://www.ncbi.nlm.nih.gov/pubmed/31127047