Ostarine / MK-2866
Ostarine or MK-2866 (CAS# 1235370-13-4) is a research chemical developed originally by Merck Inc. and now owned by GTx Inc. It is undergoing trials for Phase II (human) research. MK-2688 belongs to a class of chemicals known as SARMs or selective androgen receptor modulators. SARMs create selective anabolic activity at certain androgen receptors and not others, hence their name. Compared to testosterone, the sex hormone, the advantage of SARMs such as MK-2688 is that they do not have androgenic activity in non-skeletal-muscle tissues. MK-2866 is undergoing clinical trials for and may eventually be medically indicated and approved for prevention of cachexia, atrophy, and sarcopenia primarily in the elderly and sick population.
Testosterone and other androgenic anabolic steroids (AAS) are very effective at preventing muscle-wasting as well as increasing appetite and physical strength in humans and animal test subjects. However, AAS have a specific set of side-effects related to their non-specific androgen receptor activity that makes them contraindicated in many cases where they would otherwise be useful. Additionally, testosterone is subject to enzymatic conversion to a number of other bioactive hormones such as estrogen via the aromatase enzyme and DHT via the 5-alpha-reductase enzyme. While additional drugs may be prescribed to lower aromatase and 5-AR, or to minimize the side effects of AAS in some other fashion, testosterone is primarily only indicated for male hormone replacement therapy due to the fact that it is a problematic and complicated compound to use for its androgenic properties and the side-effects can vary greatly from individual to individual. Even primarily-anabolic AAS such as oxandrolone (Anavar), which are often used in terminally ill patients, do not entirely circumvent androgenic and other problematic side-effects.
Ostarine exerts its anabolic effects on skeletal muscle tissue almost exclusively, and therefore represents a new potential treatment option for a wide spectrum of conditions from age-related muscular atrophy (sarcopenia), AIDS or cancer-related wasting/cachexia, and even an agent to minimize atrophy during recovery periods from serious surgery or similar situations. It is effective in not only maintaining lean body mass (LBM) but actually increases it:
In the study, Ostarine met the primary endpoint of LBM, measured by a dual energy X-ray absorptiometry (DEXA) scan, by demonstrating statistically significant increases in LBM compared to baseline in both the Ostarine 1 mg and 3 mg treatment cohorts. Specifically, the change from baseline in LBM for the placebo, 1 mg and 3 mg treatment groups was 0.1 kg (p=0.874 compared to baseline), 1.5 kg (p=0.001) and 1.3 kg (p=0.045), respectively, at the end of the 16-week trial.[1]
Dr. Adrian Dobs, MD, MHS, an investigator in the Phase II trial for treatment of cancer cachexia, had the following to say about MK-2688:
Approximately half of all cancer patients suffer from the devastating effects of cancer induced muscle loss. Increasing lean body mass may improve patients' quality of life and even their response to cancer treatment. These Phase II results demonstrate the potential of a SARM to fill an important unmet need as there are currently no FDA-approved therapies available for cancer cachexia.[1]
As mentioned above as well as by Dobs, there exist few treatments for cachexia, no FDA-approved indicated treatments, and certainly no ideal treatments; the same is true of the majority of muscle-wasting conditions. Muscle-wasting related to cancer is the cause of a full 20% of cancer-related deaths, and it is likely that in related and similar conditions the instance of morbidity is equally high.[1]
As mentioned by Furuya, the effects of MK-2688 translate to anabolism in bone as well as skeletal muscle tissue, which means it could be indicated in an extremely wide variety of uses such as osteoporosis and as a concurrent treatment with drugs that reduce bone density, such as the class of cancer-treatment drugs known as selective estrogen receptor modulators:
Many efforts to produce novel drug materials maintaining a desired biological activity with an adequate tissue selectivity, which is so-called selective androgen receptor modulators (SARMs) , are being performed. As one of such efforts, studies on SARMs against bone tissues which possess a significant potential to stimulate a bone formation with reducing undesirable androgenic virilizing activities are in progress all over the world.[2]
Maddedu and Mantovani suggest in a review of candidate-drugs for cachexia that a tailored combination regimen may be more effective than any one currently-researched drug:
There are no published conclusive phase III controlled clinical trials nor general consensus about treatment approaches despite several years of coordinated efforts in basic and clinical research. Consequently, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking. The purpose of this review is to supply an update on the promising agents and/or combined approaches for the treatment of cancer cachexia. RECENT FINDINGS: The choice for cancer cachexia treatment in clinical practice is very limited: the only approved drugs in Europe are progestagens. Several drugs with a strong rationale have failed or have not shown univocal results in clinical trials: they include eicosapentaenoic acid, cannabinoids, bortezomib and anti-tumor necrosis factor (TNF)-alpha monoclonal antibody. Several emerging drugs have shown promising results but are still under clinical investigation [thalidomide, selective cyclooxygenase (COX)-2 inhibitors, ghrelin mimetics, oxandrolone, olanzapine]. Moreover, increasing knowledge of cachexia pathophysiology and preliminary clinical findings seem to suggest that a combined treatment approach may be the most effective option. SUMMARY: A number of promising new agents are currently being developed but are not as yet regarded as standard of care. They include: selective COX-2 inhibitors, ghrelin mimetics, oxandrolone, selective androgen receptor modulators (ostarine), olanzapine, anti-IL-6 antibody and an innovative approach of multitargeted combined treatment. The data reported seem to suggest that the most effective treatment for cancer cachexia may be a combination regimen rather than single-agent treatments. This is in keeping with the general consensus that cancer cachexia is a multifactorial process and, hence, a potentially effective approach should be multimodal.[3]
Cititations:
[1] “GTx Presents Phase II Ostarine (MK-2866) Cancer Cachexia Clinical Trial Results At Endocrine Society Annual Meeting.” Medical News TODAY. 6-14-2009. http://www.medicalnewstoday.com/articles/153779.php; Accessed 9-21-2010.
[2] Furuya K. [Translated title from Japanese: Bone and Men's Health. Bone selective androgen receptor modulators]. Clin Calcium. 2010 Feb;20(2):225-33.
[3] Madeddu C, Mantovani G. An update on promising agents for the treatment of cancer cachexia. Curr Opin Support Palliat Care. 2009 Dec;3(4):258-62.
Ostarine or MK-2866 (CAS# 1235370-13-4) is a research chemical developed originally by Merck Inc. and now owned by GTx Inc. It is undergoing trials for Phase II (human) research. MK-2688 belongs to a class of chemicals known as SARMs or selective androgen receptor modulators. SARMs create selective anabolic activity at certain androgen receptors and not others, hence their name. Compared to testosterone, the sex hormone, the advantage of SARMs such as MK-2688 is that they do not have androgenic activity in non-skeletal-muscle tissues. MK-2866 is undergoing clinical trials for and may eventually be medically indicated and approved for prevention of cachexia, atrophy, and sarcopenia primarily in the elderly and sick population.
Testosterone and other androgenic anabolic steroids (AAS) are very effective at preventing muscle-wasting as well as increasing appetite and physical strength in humans and animal test subjects. However, AAS have a specific set of side-effects related to their non-specific androgen receptor activity that makes them contraindicated in many cases where they would otherwise be useful. Additionally, testosterone is subject to enzymatic conversion to a number of other bioactive hormones such as estrogen via the aromatase enzyme and DHT via the 5-alpha-reductase enzyme. While additional drugs may be prescribed to lower aromatase and 5-AR, or to minimize the side effects of AAS in some other fashion, testosterone is primarily only indicated for male hormone replacement therapy due to the fact that it is a problematic and complicated compound to use for its androgenic properties and the side-effects can vary greatly from individual to individual. Even primarily-anabolic AAS such as oxandrolone (Anavar), which are often used in terminally ill patients, do not entirely circumvent androgenic and other problematic side-effects.
Ostarine exerts its anabolic effects on skeletal muscle tissue almost exclusively, and therefore represents a new potential treatment option for a wide spectrum of conditions from age-related muscular atrophy (sarcopenia), AIDS or cancer-related wasting/cachexia, and even an agent to minimize atrophy during recovery periods from serious surgery or similar situations. It is effective in not only maintaining lean body mass (LBM) but actually increases it:
In the study, Ostarine met the primary endpoint of LBM, measured by a dual energy X-ray absorptiometry (DEXA) scan, by demonstrating statistically significant increases in LBM compared to baseline in both the Ostarine 1 mg and 3 mg treatment cohorts. Specifically, the change from baseline in LBM for the placebo, 1 mg and 3 mg treatment groups was 0.1 kg (p=0.874 compared to baseline), 1.5 kg (p=0.001) and 1.3 kg (p=0.045), respectively, at the end of the 16-week trial.[1]
Dr. Adrian Dobs, MD, MHS, an investigator in the Phase II trial for treatment of cancer cachexia, had the following to say about MK-2688:
Approximately half of all cancer patients suffer from the devastating effects of cancer induced muscle loss. Increasing lean body mass may improve patients' quality of life and even their response to cancer treatment. These Phase II results demonstrate the potential of a SARM to fill an important unmet need as there are currently no FDA-approved therapies available for cancer cachexia.[1]
As mentioned above as well as by Dobs, there exist few treatments for cachexia, no FDA-approved indicated treatments, and certainly no ideal treatments; the same is true of the majority of muscle-wasting conditions. Muscle-wasting related to cancer is the cause of a full 20% of cancer-related deaths, and it is likely that in related and similar conditions the instance of morbidity is equally high.[1]
As mentioned by Furuya, the effects of MK-2688 translate to anabolism in bone as well as skeletal muscle tissue, which means it could be indicated in an extremely wide variety of uses such as osteoporosis and as a concurrent treatment with drugs that reduce bone density, such as the class of cancer-treatment drugs known as selective estrogen receptor modulators:
Many efforts to produce novel drug materials maintaining a desired biological activity with an adequate tissue selectivity, which is so-called selective androgen receptor modulators (SARMs) , are being performed. As one of such efforts, studies on SARMs against bone tissues which possess a significant potential to stimulate a bone formation with reducing undesirable androgenic virilizing activities are in progress all over the world.[2]
Maddedu and Mantovani suggest in a review of candidate-drugs for cachexia that a tailored combination regimen may be more effective than any one currently-researched drug:
There are no published conclusive phase III controlled clinical trials nor general consensus about treatment approaches despite several years of coordinated efforts in basic and clinical research. Consequently, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking. The purpose of this review is to supply an update on the promising agents and/or combined approaches for the treatment of cancer cachexia. RECENT FINDINGS: The choice for cancer cachexia treatment in clinical practice is very limited: the only approved drugs in Europe are progestagens. Several drugs with a strong rationale have failed or have not shown univocal results in clinical trials: they include eicosapentaenoic acid, cannabinoids, bortezomib and anti-tumor necrosis factor (TNF)-alpha monoclonal antibody. Several emerging drugs have shown promising results but are still under clinical investigation [thalidomide, selective cyclooxygenase (COX)-2 inhibitors, ghrelin mimetics, oxandrolone, olanzapine]. Moreover, increasing knowledge of cachexia pathophysiology and preliminary clinical findings seem to suggest that a combined treatment approach may be the most effective option. SUMMARY: A number of promising new agents are currently being developed but are not as yet regarded as standard of care. They include: selective COX-2 inhibitors, ghrelin mimetics, oxandrolone, selective androgen receptor modulators (ostarine), olanzapine, anti-IL-6 antibody and an innovative approach of multitargeted combined treatment. The data reported seem to suggest that the most effective treatment for cancer cachexia may be a combination regimen rather than single-agent treatments. This is in keeping with the general consensus that cancer cachexia is a multifactorial process and, hence, a potentially effective approach should be multimodal.[3]
Cititations:
[1] “GTx Presents Phase II Ostarine (MK-2866) Cancer Cachexia Clinical Trial Results At Endocrine Society Annual Meeting.” Medical News TODAY. 6-14-2009. http://www.medicalnewstoday.com/articles/153779.php; Accessed 9-21-2010.
[2] Furuya K. [Translated title from Japanese: Bone and Men's Health. Bone selective androgen receptor modulators]. Clin Calcium. 2010 Feb;20(2):225-33.
[3] Madeddu C, Mantovani G. An update on promising agents for the treatment of cancer cachexia. Curr Opin Support Palliat Care. 2009 Dec;3(4):258-62.
*The latter article is intended for educational / informational purposes only. THIS PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. Bodily introduction of any kind into humans or animals is strictly forbidden by law.
