Oral compounds in preclinical research: 5-Amino-1MQ, AICAR, Anastrozole, Andarine (S4), and BAM-15
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Technical analysis of oral compounds in preclinical research, including 5-Amino-1MQ, AICAR, Anastrozole, Andarine (S4) and BAM-15. Their mechanisms of action and preclinical evidence are described, emphasizing their HPLC purity and exclusive use in research.
Introduction
This technical article describes a selection of orally administered compounds that have been the object of preclinical research, highlighting their mechanisms of action and the evidence generated in studies in vitro e in vivo. The compounds to be discussed are 5-Amino-1MQ, AICAR, Anastrozole, Andarine (S4) and BAM-15. All the compounds mentioned exhibit batch purity by high-performance liquid chromatography (HPLC), guaranteed by the analytical laboratory Chromasys.
Compounds of the group
5-Amino-1MQ
5-Amino-1MQ Oral is a selective inhibitor of nicotinamide N-methyltransferase (NNMT). NNMT is a cytosolic enzyme that catabolizes S-adenosylmethionine and nicotinamide, influencing energy metabolism and methylation. Inhibition of NNMT with 5-Amino-1MQ has been explored in the context of metabolic regulation.
AICAR
AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is an adenosine analog that can be transported into the cell interior and phosphorylated to ZMP, an AMP mimetic. ZMP activates AMP-activated protein kinase (AMPK), a key enzyme in cellular energy homeostasis. AMPK activation modulates various metabolic processes.
Anastrozole
Anastrozole is a non-steroidal aromatase inhibitor. Aromatase is an enzyme that catalyzes the conversion of androgens to estrogens. The inhibition of this enzyme reduces estrogen levels, which has been a point of interest in various preclinical studies related to hormone-dependent tissues.
Andarine (S4)
Andarine (S4) it is a selective androgen receptor modulator (SARM). SARMs bind to androgen receptors with tissue selectivity, exhibiting agonist activity in some tissues and antagonist activity in others, unlike steroidal androgens, which tend to have broader and less selective effects. Andarine has been studied for its effects on muscle and bone tissue in preclinical models.
BAM-15
BAM-15 it is an uncoupler of mitochondrial oxidative phosphorylation. It acts by dissipating the proton gradient across the inner mitochondrial membrane, allowing protons to return to the mitochondrial matrix without passing through ATP synthase. This process uncouples respiration from ATP production, generating heat and increasing energy expenditure. This has been studied in contexts of metabolic and energy regulation.
Compared mechanisms
Although each compound has a unique mechanism of action, they can be grouped in terms of their main molecular targets:
- Metabolic modulators: 5-Amino-1MQ (an NNMT inhibitor), AICAR (an AMPK activator) and BAM-15 (a mitochondrial uncoupler) directly influence energy metabolic pathways. 5-Amino-1MQ affects methylation and nicotinamide metabolism, AICAR simulates a low-energy state by activating AMPK, and BAM-15 increases energy expenditure through thermogenesis.
- Hormonal modulators: Anastrozole (aromatase inhibitor) and Andarine (SARM) act on the endocrine system. Anastrozole reduces estrogen biosynthesis, while Andarine selectively modulates signaling through the androgen receptors.
Preclinical evidence
Preclinical research has provided valuable information on these compounds:
- 5-Amino-1MQ: Studies in vitro e in vivo have demonstrated that the inhibition of NNMT with 5-Amino-1MQ can influence adipogenesis and lipid metabolism. For example, in murine models, it has been observed that 5-Amino-1MQ can attenuate weight gain and improve metabolic parameters on high-fat diets (Neelakantan et al., 2018).
- AICAR: Numerous studies in vivo have investigated the role of AICAR in AMPK activation and its metabolic consequences. In animal models, AICAR administration has been shown to improve insulin sensitivity, increase fatty acid oxidation and improve mitochondrial function in various tissues, including skeletal muscle (Merrill et al., 1997).
- Anastrozole: The inhibition of aromatase with anastrozole has been extensively studied in models of estrogen-dependent breast cancer, where it has been demonstrated to be effective in reducing tumor growth through the decrease of estrogen levels (Baum et al., 2002).
- Andarine (S4): Preclinical evidence in animal models suggests that Andarine may selectively increase muscle mass and bone mineral density, without the side effects associated with steroidal androgens in other tissues. Andarine has been observed to improve muscle strength and body composition in rats (Kearbey et al., 2007).
- BAM-15: Recent research has explored the potential of BAM-15 in weight reduction and metabolic improvement. Rodent studies have indicated that BAM-15 can induce non-shivering thermogenesis, promote fat oxidation, and protect against weight gain and insulin resistance in diet-induced obesity models (Alexopoulos et al., 2020).
Laboratory handling
These compounds are strictly for laboratory research use and are not intended for human use. It is essential to follow laboratory chemical safety and handling guidelines. The HPLC purity characteristics are guaranteed by the analytical laboratory Chromasys, ensuring reliability in experimental studies.
References
Material for research use only. Verified primary sources (PubMed/CrossRef) supporting the claims of this article:
- Alexopoulos SJ, Chen SY, Brandon AE, Salamoun JM, Byrne FL, et al. Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice. Nat Commun. 2020;11(1):2397. doi:10.1038/s41467-020-16298-2. PMID 32409697. (animal)
- Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JGM, Sahmoud T; ATAC Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002;359(9324):2131-2139. doi:10.1016/S0140-6736(02)09088-8. PMID 12090977. (humano)
- Kearbey JD, Gao W, Narayanan R, Fisher SJ, Wu D, Miller DD, Dalton JT. Selective androgen receptor modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats. Pharm Res. 2007;24(2):328-335. doi:10.1007/s11095-006-9152-9. PMID 17063395. (animal)
- Merrill GF, Kurth EJ, Hardie DG, Winder WW. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol. 1997;273(6 Pt 1):E1107-E1112. doi:10.1152/ajpendo.1997.273.6.E1107. PMID 9435525. (animal)
- Neelakantan H, Vance V, Wetzel MD, Wang HL, McHardy SF, Finnerty CC, Hommel JD, Watowich SJ. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochem Pharmacol. 2018;147:141-152. doi:10.1016/j.bcp.2017.11.007. PMID 29155147. (animal)
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See also
- Oral Research Compounds: A Review of BPC-157, TB-500, Cabergoline, GW-501516, and Clenbuterol
- Oral Hormonal Modulators and Neuromodulators: A Preclinical Review
- Oral Research Compounds: A Review of Finasteride, Isotretinoin, KPV, LGD-4033 and Methylene Blue
- Oral Agents with Potential Research Use: A Comparative Review
Literature on the compounds cited
- Sobre 5-Amino-1MQ Oral: Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice (Neelakantan, et al. · Biochemical Pharmacology · 2018) PMID 29155147.
- Sobre 5-Amino-1MQ Oral: Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice (Dimet-Wiley, et al. · Scientific Reports · 2022) PMID 35013352.
- Sobre 5-Amino-1MQ Oral: Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. (Babula JJ, et al. · Diabetes Obes Metab · 2024) PMID 39161060.
- Sobre Andarine (S-4): Detection of the arylpropionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product. (Thevis M, et al. · Drug Test Anal · 2009) PMID 20355219.
- Sobre Andarine (S-4): Mass spectrometric characterization of urinary metabolites of the selective androgen receptor modulator andarine (S-4) for routine doping control purposes. (Thevis M, et al. · Rapid Commun Mass Spectrom · 2010) PMID 20623476.
- Sobre Andarine (S-4): Selective Androgen Receptor Modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats (Kearbey, et al. · Pharmaceutical Research · 2007) PMID 17063395.
