S-23 Ultrabolic SARMs Gel 20MG (Packs of 5, 10 or 30)
$16.00 – $86.00
S-23 SARM is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.
*APPLICATION: SARM GEL IS ORAL (NOT TOPICAL)
- Additional information
S-23 SARM Gels
|Other Names||S23, S 23, CCTH-methylpropionamide, UNII-XDK89456WM, SCHEMBL2816704, SSFVOEAXHZGTRJ-UHFFFAOYSA-N, BCP30652|
|Purity||≥99% Pure (LC-MS)|
|Application||SARM GEL IS ORAL (NOT TOPICAL)|
|Liquid Availability|| 30mL liquid Glycol (20mg/mL, 600mg bottle) |
30mL liquid Poly-Cell™ (20mg/mL, 600mg bottle)
60mL liquid Glycol (20mg/mL, 1200mg bottle)
60mL liquid Poly-Cell™ (20mg/mL, 1200mg bottle)
|Powder Availability||1 gram|
|Gel Availability||20 milligrams|
|Storage||Store in cool dry environment, away from direct sunlight.|
|Terms||All products are for laboratory developmental research USE ONLY. Products are not for human consumption.|
What is S-23?
S-23, also referred to as, (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro,4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide, has been shown to act as a selective androgen receptor modulator (SARM). The SARM is best known for its potential to act as a male contraceptive, increase female libido, promote anabolic activity in skeletal muscles and bone tissue, and act as a partial agonist to the androgen receptor.
Main Research Findings
1) S-23 is capable of treating muscle atrophy induced by prolonged glucocorticoid usage as well as hypogonadism.
2) Ovariectomized female rats experience an increase in sexual motivation following treatment with S-23.
1) The research team of Jones et. Al examined the potential of S-23 to treat muscle atrophy induced hypogonadism as well as chronic corticoid usage. Male Sprague-Dawley rats aged 5-6 weeks old and weighing 229-238 g were obtained from Harlan Bioproducts for Science. Food and water was available ad libitum and the animals were kept on a strict 12-hour dark, 12-hour light cycle. Before and after treatment the research team measured body fat, lean body mass (LBM), fluids, and total water via MRI screening. The rats were then randomized according to LBM and assigned to one of four groups. Animals were subcutaneously injected with a treatment dose of the compound of interest over an experimental period of 8 days. Group 1 was defined as the control group and was administered only a vehicle while groups 2-4 were administered 600 ug/kg of DEX; groups 3 and 4 received the same dose of DEX as well as 25 mg/kg of testosterone propionate (TP), or S-23 .
24 hours after the last dose the animals were weighed and euthanized. The ventral prostate and seminal vesicles were extracted and weighted while the levator ani, gastrocnemius, extensor digitorum longus (EDL), and soleus muscle were extracted, weight and segmentally preserved in RNAlater for gene expression and protein expression analysis. Serum testosterone was analyzed through the use of liquid chromatography and tandem mass spectrometry. Cell cultures were taken from the myoblasts of the mouse skeletal muscle cell line and cultured in a growth medium composed of DMEM, 10% FBS, 100 U/ml penicillin, and 100 ug/ml streptomycin.
Additionally, quantitative real-time PCR was performed by seeding mouse skeletal muscle cells into six-well plates in medium at a density of 1 million cells/wells, followed by an 8 hour recovery period. After 24 hours cells were transduced with 250 virus particles/well and incubated for another 24 hours. After incubation cells were treated with the compound of interest and incubated for another 24 hours before muscle sample analysis took place. RT PCR was followed by Western blotting analysis. The mouse skeletal muscle cells were seeded into 10 cm dishes in a medium at a density of 2.5 million cells/dish. Cells were transduced and treated in the same manner as the RT PCR, and were washed with PBS before the protein was extracted in a buffer solution and subjected to further analysis. Finally, statistical analysis was performed through the use of single-factor ANOVA and Dunnet’s multiple comparison test .
An additional group of male Sprague-Dawley rats was obtained from Harlan Bioproducts in order to conduct a time-course study. 24 hours before drug treatment the animals were orchidectomized via scrotal incision. S-23 was then administered subcutaneously at a dose rate of 1 mg per day. Intact and castrated muscles were administered a vehicle treatment and used as the control groups; all animals were treated for 3, 7, 19, 14, 21, or 28 days. 24 hours after the last treatment the animals were weighed and euthanized while the ventral prostate, seminal vesicles, levator ani, gastrocnemius, EDL, and soleus muscles were extracted, weighed, and preserved for further gene expression analysis. These animals were subjected to the same cell culturing, RT PCR, Western blotting, and statistical analyses, as the primary experimental group .
2) Researchers Jones et. Al conducted a study examining how sexual motivation can be directly influenced by various qualities of the popular SARM, S-23. Experimentation began by observing in vitro binding affinity of the androgen receptor. Initially, the ligand binding domain (LBD) of the androgen receptor was fused with glutathione S-transferase (GST); the results compound was expressed as a recombinant protein labeled as AR GST-LBD. Following proper preparation of all samples, chemical purities were determined through the use of nuclear magnetic resonance (NMR) and mass spectroscopy.
Increasing concentrations of the compounds were incubated with 4 nM [^3H]MIB and AR GST-LBD over an 18 hour period. In order to determine total and nonspecific binding, proteins were incubated with and without a high concentration of unlabeled MIB. All filter plates were harvested, washed three times with an ice-cold buffer solution, and allowed to dry to completion at room temperature. The specific binding of [^3H]MIB at varying concentrations was determined by subtracting nonspecific binding of [^3H]MIB and expressed as a percentage of specific binding in the absence of a competitor. The concentration of the compound of interest that reduced the specific binding of [^3H]MIB by 50% was determined by nonlinear regression using the standard four-parameter logistic curve. The research team was then able to calculate the equilibrium binding constant Ki while all binding affinities of the compounds of interests were recorded and compared to the results of dihydrotestosterone (DHT) .
The next step of the study was to examine in vitro transcriptional activation mediated by androgen and estrogen receptors in a cotransfection system. Human embryonic kidney (HEK) 293 cells (ER-alpha) or CV-1 cells (AR) were transfected in 15 cm dishes using Lipofectamine and maintained in serum-free Dulbecco’s minimal essential medium. Each dish of cells was transfected with 45 ug of GRELuc, I ug of CMVLuc, and 2.5 ug of CMVhAR, CMVhER-alpha, or CMVhER-beta expression vector. Following transfection the cells were allowed to recover over the course of 12 hours and were then seeded in 24-well plates in Dulbecco’s minimal essential medium containing 2% charcoal-stripped fetal bovine serum. The cells recovered for an additional 8 hours before drug treatment began.
The agonist activity of the test compounds was compared to the transcriptional activation induced by 1 nM of DHT or estradiol (E2). The cells were left untreated for 24 hours before being washed with Dulbecco’s phosphate-buffered saline (PBS) and lysed with 50 ul/well of passive lysis buffer for 30 minutes. Luciferase assays were completed using 25 ul of the cell lysate. Transcriptional activity was calculated in each well by determining the ratio of luciferase activity to Renilla luciferase activity; this calculation method was used in order to avoid variations in cell number and transfection efficiency .
The final in vitro examination allowed the research team to observe the interaction between the amino terminus and carboxyl terminus. The amino terminus-carboxyl terminus (N-C) interaction of the AR is identified by a mammalian two-hybrid assay. The AR cells were maintained and transfected while each cell dish was transfected with 45 ug of pG5Luc, 2.5 ug of pACT AR-N-terminal domain, 2.5 ug of pBind AR-LBD, and 1 ug of CMVLuc. Luciferase activity increases as a result of a facilitated interaction between the N-terminal domain and the LBD, as well as the close proximity of the activating domain to the DNA binding domain. The activity of the compounds were compared to the interaction induced by 10 nM of DHT. Luciferase assays were completed according to protocol while N-C interaction induced by each compound of interest was expressed as a percentage of the interaction induced by 10 nM of DHT .
The in vivo portion of the study utilized male and female Sprague-Dawley rats. All subjects were given ad libitum access to food and water and were maintained on a 12 hour light and 12 hour dark schedule. All animal studies were conducted in accordance with the protocols approved by the Institutional Laboratory Animal Care and Use Committee and the University of Tennessee (male subject studies) or Ohio State University (female subject studies).
Castrated male rats were the first subjects observed in order to determine the in vivo pharmacologic activity of each AR ligand. The animals were orchidectomized 24 hours before the start of drug treatment, followed by 2 weeks of daily subcutaneous injection of 1 mg/kg of the test compound. Before daily administration each ligand was dissolved in a vehicle solution containing DMSO and PEG300. Two additional groups, one castrated one intact, received only a vehicle dose and were used as control groups. 24 hours after the last dose the animals were euthanized in order to extract the ventral prostate, seminal vesicles, and levator ani muscle. The three organ weights were recorded and normalized to total body weight while the weights of the prostate and seminal vesicles were used as an indicator of androgenic activity. The levator ani muscle was observed to determine the anabolic effects of the drug treatment .
Ovariectomized female rats were treated with S-23 in order to observe sexual motivation in female rats The test subjects were ovariectomized via dorsal incision 24 hours before daily subcutaneous injection of the drug treatment began. Two additional groups, one ovariectomized one intact, received a vehicle treatment only to act as a control group. The compounds of interest were dissolved in a vehicle containing DMSO/PEG300 and administered for 14 days, daily at a dose of 3 mg/kg. Testosterone propionate was administered as a positive control and was coadministered with an antiandrogen in order to highlight the importance of AR activation .
A three-compartment chamber with wood shaving covering the floor was the primary apparatus used for behavioral testing. All testing was conducted 12 hours after the last treatment dose was given, typically taking place early during the 12 hour dark period under dim red light. Sexually experienced female rats were allowed to acclimate to the chamber in three 15-minute periods; two the week before behavioral testing and one immediately before testing. Exploration of the chamber took place in the absence of male rat stimulus. Four hours before behavioral testing the female rats were subcutaneously administered a 0.1 mg dose of progesterone to support and facilitate sensual behavior. After the last 15 minute acclimation period the female subjects were restricted to the central compartment while one intact and one castrated male rat were led into the lateral compartments.
Opaque partitions were put in place and the rats were allowed to habituate with each other for 5 minutes. After 5 minutes the partitions were removed and the female rat was able to roam freely for a 30 minute behavioral testing period. However, the males’ larger size forced them to remain in the lateral compartments. Duration of time and compartment entries were measured each time the female rat passed through to a different compartment of the chamber. Following the behavior testing the animals were euthanized 24 hours after the last treatment dose was injected while the uterus was extracted and weighed .
1) First, the research team of Jones et. Al began the study by AR-transducing mouse skeletal muscle cells and incubating overnight with DEX in order to induce atrophy. DEX incubation led to a 6.5-fold increase in expression of MAFbx mRNA. When the samples were treated with TP or S-23, up-regulation of mRNA expression was significantly inhibited. DEX incubation also led to a 13-fold decrease in the expression of IGF-1 mRNA; this response was inhibited by TP and S-23 at concentrations greater than 1 nM. Adding DEX to the mouse skeletal muscle cells led to the reduction in phosphorylation of proteins involved in the PI3K/Akt pathways.
Intact male rats experienced a significant reduction in total body weight after administration of DEX. Cotreatment with TP and S-23 inhibited the overall effects of DEX on body weight. DEX treatment also led to a 5% reduction in LBM while TP only partially inhibited this affection. DEX also significantly reduced prostate and seminal vesicle size. When coadministering an androgen treatment, the weights of these aforementioned tissues significantly increased. The levator ani muscle was extracted in order to measure weight changes in response to DEX. Results reported that weight of the levator ani decreased by 52% when DEX was administered. This decrease in weight was inhibited by TP and S-23 administration; the weight of the muscle was similar to that in the intact control group. In response to DEX treatment the gastrocnemius muscle weight was reduced by 37%, while the EDL also reduced in size by 34%. It is important to note that when TP and S-23 were administered, no attenuation of the effects were observed. The soleus muscle also experienced a decrease in size following DEX administration, however, this response was inhibited by S-23 but not TP .
Figure 4: Effects of treatment on body weight, LBM, and androgenic/anabolic activity. A) average body weight, B) absolute change in LBM, C) normalized prostate weights, D) seminal vesicles, E) levator ani muscle, F) gastrocnemius muscle G) EDL, H) soleus muscle
When administering DEX to intact animals, the subjects experienced an upregulation in MAFbx mRNA in the levator ani, gastrocnemius, EDL, and soleus muscles. Coadministration of TP and S-23 inhibited upregulation of mRNA expression in the levator ani while expression in the gastrocnemius, EDL, and soleus was significantly inhibited by S-23 and only slightly by TP. A similar trend was observed with the expression of . TP and S-23 inhibited upregulation of mRNA expression in the levator ani, while only S-23 led to a significant inhibition in expression in the gastrocnemius, EDL, and soleus muscles. Levels of IGF-1 were decreased by DEX administration, specifically in the gastrocnemius, EDl, and soleus by 3-, 6.5, and 5.5-fold, respectively. The levator ani muscle did not experience any changes in IGF-1 expression. Again, S-23 was more effective than TP in inhibiting the expression of IGF-1 in the gastrocnemius, EDL, and the soleus muscle .
Figure 5: Effects of treatment on gene expression. A) MAFbx, B) MuRF1, C) IGF-1
In regards to the secondary experimental group examining the effects of time and treatment with S-23 in castrated rats. All subjects were castrated in order to induce hypogonadism-related muscle atrophy. 3 days post-orchiectomy, the prostate and levator ani sizes were reduced by 67 and 79% of the intact control group, respectively. Over the course of 14 days both tissues continued to decrease in weight. When S-23 was administered to the orchidectomized animals, the weight of both the prostate and the levator ani were maintained. The weight of each organ continued to increase in the animals treated with the SARM for 28 days. In terms of gene expression, castration led to a 40-fold increase in MAFbx mRNA expression at day 3, however, this increase levels off by day 14. S-23 inhibits the upregulation of mRNA expression at 3, 7, and 10 days, but no further changes were observed past day 14. Additionally, the researchers thought it was important to note that IGF-1 was down-regulated in response to castration but his response was inhibited by S-23 .
Figure 6: Effects of time and S-23 on androgenic and anabolic activity in the tissues of castrated male rats. A) Body weights before and after treatment, B) normalized prostate weight of castrated control and S-23 treated animals, C) normalized levator ani weight of castrated control and S-23 treated animals, D) expression change of muscle atrophy marker MAFbx in orchidectomized subjects, E) expression change of muscle atrophy marker MAFbx in orchidectomized subjects each day, F) Fold expression change of muscle hypertrophy marker IGF-I, in orchidectomized animals compared to the control, and G) Fold expression change of muscle hypertrophy marker IGF-I in S-23 treated animals compared to orchidectomized animals each day
2) The in vitro portion of the study conducted by Jones et. Al reported that S-23 led to a significant increase in transcription activation mediated by the androgen receptors when compared to the transcriptional activity elicited by 1 nM of DHT. The in vivo pharmacological portion of the study found that the weight of the prostate, seminal vesicles, and levator ani decreased after the animals were castrated. Additionally, androgen-dependent organs experienced a dose-dependent increase in weight when S-23 was administered to the castrated animals. When the animals were given 1.0 mg/day of S-23 the weight of the prostate and seminal vesicles were maintained at weights equal to or greater than that of intact animals. Weight of the levator ani was selectively maintained in doses as low as 0.1 mg/day. The Emax of S-23 in the prostate, seminal vesicles, and levator ani muscle was found to be 138 ± 21, 144 ± 1, and 129 ± 4%, respectively .
Figure 4: Androgenic and anabolic activity of S-23 in intact male rats
Mating trials took place at the end of the treatment period in order to assess the efficacy of S-23 as a male contraceptive. Estradiol benzoate was administered in addition with the SARM in order to ensure sufficiently restored mating behavior in the castrated male rats. Results reported that the weight of the levator ani muscle in castrated male rats was maintained at doses between 0.1 and 0.3 mg/day. Researchers observed groups 1, 2, 4, and 5: vehicle, EB only, EB + 0.1 mg S-23, and EB + 0.3 mg S-23, respectively. There were no observed differences in the number of mounts, mount latency, number of intromissions, or intromission latency between the four groups, allowing the research team to conclude that EB alone and EB + S-23 were able to maintain normal sexual behavior relative to the control group.
Contraception efficacy was measured by the fertility rate of the male rat included in the mating trials. Results found that all male rats treated with EB + 0.1 mg of S-23 were infertile while only one of six male rats treated with EB + 0.3 mg of S-23 was fertile. In terms of spermatogenesis, it was first evaluated by counting the number of homogenization-resistant advanced spermatids from control and experimental rats. There were no differences in mean sperm count between the intact control animals and the EB-treated animals. When EB was administered with S-23, the SARM elicited a biphasic effect on sperm count in the testis. This response is directly related to the androgenic activity of drug treatment in the sexual organs. Spermatogenesis was significantly inhibited in the treatment group receiving EB + 0.1 mg/day of S-23. Four out of the six animals in the treatment group exhibited no sperm in the testis while sperm count was barely detectable in the other two animals .
FIgure 5: Testicular sperm concentrations
After the test subjects were euthanized the body weight of each animal was recorded. All EB-treated groups exhibited significantly lower body weight and prostate weight, however, total body BMD was greater than that in the intact, vehicle-treated group. The animals that received S-23 experienced a decrease in the weight of the testis while weight of the levator ani muscle remained unchanged. Treatment with EB alone did not significantly change fat mass in comparison to the intact control group. When EB was administered with S-23 fat mass was shown to decrease in a dose-dependent manner; doses of 0.3 mg/day of S-23 and higher, led to a significant diminishment of fat mass in comparison to the intact control group. Overall, the researchers were able to conclude that S-23 treatment in addition to EB administration, effectively decreases fat mass .
Figure 6: dose-dependent changes in fat mass elicited by S-23
**LAB USE ONLY**
*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).
 Jones A, Hwang DJ, Narayanan R, Miller DD, Dalton JT. Effects of a novel selective androgen receptor modulator on dexamethasone-induced and hypogonadism-induced muscle atrophy. Endocrinology. 2010 Aug;151(8):3706-19. doi: 10.1210/en.2010-0150. Epub 2010 Jun 9. PMID: 20534726.
 Jones A, Hwang DJ, Duke CB 3rd, He Y, Siddam A, Miller DD, Dalton JT. Nonsteroidal selective androgen receptor modulators enhance female sexual motivation. J Pharmacol Exp Ther. 2010 Aug;334(2):439-48. doi: 10.1124/jpet.110.168880. Epub 2010 May 5. PMID: 20444881; PMCID: PMC2913771.
S-23 is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.
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