RAD-140 (Testolone)
| Chemical Information: | |
|---|---|
| Chemical Name: | (2-chloro-4-((2-(4-cyanophenoxy)-2-methylpropyl)amino)-3-methylphenyl)(4-cyanophenyl)methanone |
| CAS Number: | 1182367-47-0 |
| Molecular Formula: | C₂₀H₁₆ClN₅O₂ |
| Molecular Weight: | 393.83 g/mol |
| Purity: | ≥99% (as confirmed by Liquid Chromatography-Mass Spectrometry, LC-MS) |
RAD-140 (Testolone): An In-Depth Guide for Animal Research
RAD-140, commonly known as Testolone, is a selective androgen receptor modulator (SARM) developed as an alternative to traditional anabolic steroids. It has garnered attention for its anabolic effects on muscle and bone tissues while minimizing the androgenic side effects often associated with steroid use. Originally developed by Radius Health, Inc., RAD-140 was designed to treat muscle-wasting disorders, osteoporosis, and potentially certain forms of cancer. This profile delves into the development, mechanism of action, applications, and ongoing research into this compound.
Development and Purpose
RAD-140 was developed in response to the need for anabolic compounds that target muscle and bone tissue without significant systemic side effects. Traditional anabolic steroids, while effective, carry risks such as liver toxicity, cardiovascular issues, and prostate enlargement. The key objectives in developing RAD-140 were:
Selective Anabolic Activity:
Target androgen receptors in skeletal muscle and bone tissue while sparing other organs such as the prostate and liver.
Treatment of Muscle-Wasting Disorders:
Provide a therapeutic option for cachexia, sarcopenia, and muscle atrophy caused by chronic illnesses or aging.
Bone Health:
Strengthen bone density and reduce fracture risk, making it a potential candidate for osteoporosis treatment.
Cancer Therapy:
Investigate its potential to inhibit androgen receptor-positive breast cancer cell growth.
Mechanisms of Action
TB-500 exerts its effects through multiple interconnected biological pathways, which collectively enhance tissue repair, reduce inflammation, and promote overall recovery. Below is an expanded breakdown of its key mechanisms:
1. Actin Regulation
TB-500 is a synthetic peptide that mimics the action of thymosin beta-4, which is a natural regulator of actin. Actin is a critical cytoskeletal protein involved in numerous cellular processes, including:
- Cell Migration: By upregulating actin, TB-500 facilitates the migration of cells such as fibroblasts, keratinocytes, and endothelial cells to the site of injury. This cell movement is essential for wound closure and tissue repair.
- Cellular Integrity: Actin plays a vital role in maintaining the structural stability of cells, particularly during tissue remodeling or stress. TB-500’s ability to modulate actin dynamics ensures efficient cellular function under challenging conditions.
2. Angiogenesis
TB-500 has been shown to stimulate angiogenesis, the process of new blood vessel formation, which is pivotal for:
- Oxygen Delivery: Ensuring an adequate supply of oxygen to hypoxic (low-oxygen) tissues.
- Nutrient Transport: Facilitating the delivery of essential nutrients and removal of metabolic waste from the injury site.
- Healing Acceleration: Enhanced vascularization allows for faster tissue regeneration in scenarios such as tendon injuries, myocardial repair, or skin wounds.
- This angiogenic effect is thought to be mediated through the upregulation of vascular endothelial growth factor (VEGF), a key protein in blood vessel formation.
3. Anti-Inflammatory Effects
One of TB-500’s significant therapeutic benefits is its ability to modulate inflammatory responses:
- Reduction of Pro-Inflammatory Cytokines: TB-500 suppresses the release of cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), both of which are associated with chronic inflammation and delayed healing.
- Optimized Healing Environment: By reducing inflammation, TB-500 minimizes tissue swelling and pain while promoting the recruitment of reparative cells to the site of injury.
- Immune Modulation: TB-500 can modulate the immune response, helping to prevent overreaction of the immune system, which could exacerbate tissue damage.
4. Enhanced Cellular Survival and Migration
Research suggests that TB-500 activates integrin-linked kinase (ILK), a protein involved in cell survival and migration pathways. By influencing ILK:
- Apoptosis Prevention: TB-500 helps protect cells from programmed cell death in injury or stress conditions.
- Tissue Regeneration: It supports the migration of stem cells and progenitor cells to areas requiring repair, aiding in the regeneration of damaged or lost tissue.
5. Cytoprotective Properties
TB-500 demonstrates protective effects on various cell types, including cardiac, neural, and epithelial cells. These properties are vital for:
- Cardiac Repair: Reducing the extent of myocardial damage in heart injury models.
- Neurological Support: Limiting oxidative stress and improving neural cell survival in brain injury scenarios.
Applications in Animal Research
1. Muscle Growth and Recovery
RAD-140 has demonstrated potent anabolic effects in animal models, making it a valuable tool for studying muscle-wasting conditions. Rodents treated with RAD-140 exhibited significant increases in lean muscle mass and strength without adverse effects on reproductive tissues.
2. Bone Health
Animal studies have shown RAD-140’s efficacy in increasing bone mineral density and strength. It is particularly useful in models of osteoporosis, where it helps reduce fracture risk and supports bone repair.
3. Cancer Research
Preclinical studies suggest RAD-140 may inhibit the growth of androgen receptor-positive breast cancer cells. This property makes it a candidate for further exploration in cancer therapy research.
4. Neuroprotective Effects
Research indicates RAD-140 may protect brain cells from oxidative stress and damage. This potential neuroprotective effect is under investigation for conditions like Alzheimer’s and Parkinson’s diseases.
Dosage and Administration in Research
RAD-140 is typically administered orally in research studies. The dosing varies based on the animal model and research objectives. Commonly reported dosages include:
- Low Dose: 1 mg/kg/day for exploratory studies.
- Moderate Dose: 5 mg/kg/day for anabolic and muscle growth research.
- High Dose: 10 mg/kg/day, used in intensive studies with careful monitoring for systemic effects.
Research durations range from 4 to 12 weeks, depending on the experimental design and goals.
Safety Profile in Research
RAD-140 has shown a favorable safety profile in preclinical studies, with minimal side effects at therapeutic doses. However, certain considerations include:
Testosterone Suppression:
High doses or prolonged use may temporarily suppress endogenous testosterone production, which typically normalizes after discontinuation.
Liver Enzyme Elevation:
Some studies report mild elevations in liver enzymes, suggesting the need for monitoring during research.
Prostate Sparing:
Unlike traditional steroids, RAD-140 shows minimal impact on prostate weight, indicating reduced androgenic side effects.
Clinical Development and Current Status
RAD-140 has undergone Phase I clinical trials to evaluate its safety, tolerability, and pharmacokinetics in humans. These trials indicated a promising safety profile and potential efficacy in muscle-wasting disorders. However, as of now, RAD-140 remains an investigational compound and is not approved for clinical use.
Recent Research and Findings
Muscle-Wasting Conditions:
RAD-140 has shown significant muscle-preserving effects in cachexia models, making it a candidate for treating muscle atrophy in chronic illnesses.
Cancer Studies:
A study published in Clinical Cancer Research demonstrated RAD-140’s ability to inhibit AR-positive breast cancer cell growth, offering a potential therapeutic avenue.
Bone Health:
Animal studies highlighted its role in improving bone density and reducing fracture risk in osteoporotic models.
Neuroprotection:
Emerging evidence suggests RAD-140 may have protective effects on neurons, potentially reducing damage in neurodegenerative diseases.
Legal and Ethical Considerations
RAD-140 is classified as a research chemical and is not approved for human use by regulatory agencies such as the FDA or EMA. It is banned by the World Anti-Doping Agency (WADA) for use in competitive sports due to its performance-enhancing effects. Researchers must adhere to strict ethical guidelines and use RAD-140 solely for legitimate scientific purposes in controlled laboratory settings.
Conclusion
RAD-140 (Testolone) represents a promising advancement in selective androgen receptor modulators, offering potential applications in muscle-wasting disorders, osteoporosis, and cancer research. Its selective mechanism of action minimizes systemic side effects, making it a valuable tool in preclinical studies.
RAD-140 continues to provide insights into androgen receptor biology and its potential therapeutic applications as research progresses, underscoring its importance in the scientific community.
References
- Leung K, Yaramada P, Goyal P, Cai CX, Thung I, Hammami MB. RAD-140 Drug-Induced Liver Injury. Ochsner J. 2022 Winter;22(4):361-365. doi: 10.31486/toj.22.0005. PMID: 36561105; PMCID: PMC9753945.
- Anusha Jayaraman, Amy Christensen, V. Alexandra Moser, Rebekah S. Vest, Chris P. Miller, Gary Hattersley, Christian J. Pike, Endocrinology, Volume 155, Issue 4, 1 April 2014, Pages 1398–1406, https://doi.org/10.1210/en.2013-1725
- Miller CP, Shomali M, Lyttle CR, O’Dea LS, Herendeen H, Synthesis, and Preclinical Characterization of the Selective Androgen Receptor Modulator (SARM) RAD140. ACS Med Chem Lett. 2010 Dec 2;2(2):124-9. doi: 10.1021/ml1002508. PMID: 24900290; PMCID: PMC4018048.
- LoRusso P, Hamilton E, Ma C, Vidula N, Bagley RG, Troy S, Annett M, Yu Z, Conlan MG, Weise A. A First-in-Human Phase 1 Study of a Novel Selective Androgen Receptor Modulator (SARM), RAD140, in ER+/HER2- Metastatic Breast Cancer. Clin Breast Cancer. 2022 Jan;22(1):67-77. doi: 10.1016/j.clbc.2021.08.003. Epub 2021 Aug 20. PMID: 34565686.
