Research Disclaimer: RAD-140 is sold exclusively for in-vitro and laboratory research use. Not for unsupervised use. This content does not constitute medical advice.
RAD-140 (testolone; Radius Health) is a non-steroidal selective androgen receptor modulator (SARM) with high AR binding affinity (~7× testosterone) and preferential anabolic activity in muscle vs. androgenic activity in prostate. Developed as a potential treatment for breast cancer and muscle wasting, RAD-140 has become one of the most studied SARMs in preclinical research due to its favorable in vitro selectivity profile, oral bioavailability, and significant anabolic efficacy in rodent models. Understanding its mechanism of selectivity is central to SARM research.
Table of Contents#
- SARM Concept: Tissue Selectivity Mechanism
- RAD-140 Structure and AR Binding
- Pharmacokinetics
- Preclinical Efficacy Data
- Neuroprotective Effects
- HPTA Suppression Profile
- Research Protocols
- Key References
SARM Concept: Tissue Selectivity Mechanism#
Traditional anabolic steroids activate AR in all tissues equally → both anabolic (muscle, bone) AND androgenic (prostate, skin, HPT axis suppression) effects.
SARMs achieve tissue selectivity through:
1. Coactivator recruitment specificity:
- Different AR conformations (induced by different ligands) recruit different coactivators
- Muscle: expresses SRC-3/GRIP-1 coactivators → SARM-induced AR conformation efficiently recruits these → anabolic transcription
- Prostate: expresses SRC-1 coactivators → SARM-induced AR conformation less efficiently recruits these → less androgenic transcription
2. AR expression differences:
- Tissues with very high AR expression (levator ani) respond to even partial AR agonists
- Tissues with moderate AR expression (prostate) require higher AR occupancy and more efficient coactivator recruitment
3. Local metabolism differences:
- Steroidal androgens: converted to DHT by 5α-reductase in androgenic tissues → amplified androgenic response
- Non-steroidal SARMs: not substrates for 5α-reductase → no DHT amplification → reduced androgenicity in prostate/skin
RAD-140 Structure and AR Binding#
RAD-140 is a triazine-based compound:
- Non-steroidal (no steroid ring backbone)
- Not a substrate for 5α-reductase → no conversion to DHT equivalent
- Not aromatized → no estrogenic activity
- MW ~393 Da; orally bioavailable
AR binding:
- Relative AR binding affinity: ~7× testosterone (very high for a SARM)
- AR binding induces a specific coactivator-interaction surface on AR helix 12 → differs from testosterone's induced conformation → tissue-selective coactivator recruitment
- Ki at AR: ~1–3 nM (vs. testosterone ~5 nM, DHT ~0.5 nM)
In vitro anabolic:androgenic selectivity:
- Cell-based assay using myocyte and prostate cell lines: RAD-140 shows ~10:1 preference for myocyte transcriptional activation over prostate
- Hershberger assay: A:A ratio ~90:1 (highly selective; levator ani / ventral prostate)
This extremely high A:A ratio (highest among major research SARMs) is RAD-140's defining pharmacological characteristic.
Pharmacokinetics#
| Parameter | Value |
|---|---|
| Oral bioavailability | ~80% (estimated from preclinical) |
| t½ (human) | ~60 hours (very long; accumulates with daily dosing) |
| t½ (rat) | ~60 hours |
| Tmax | ~4 hours |
| Metabolism | Hepatic (CYP enzymes — not fully characterized) |
| Protein binding | High |
Long t½ implications for research:
- Once-daily dosing maintains high steady-state concentrations
- Steady-state requires ~10 days
- After cessation: slow washout (~1–2 weeks to full clearance)
- For studies with drug holidays or recovery phases: plan for slow drug clearance
Preclinical Efficacy Data#
Anabolic effects#
From peer-reviewed studies and Radius Health preclinical data:
-
Castrated male rats: RAD-140 0.1–10 mg/kg/day × 28 days
- Levator ani: restored to intact control levels at 0.3 mg/kg/day
- Ventral prostate: minimal stimulation even at 10 mg/kg/day
- A:A ratio: ~90:1 (vs. testosterone propionate = 1:1 reference)
-
Body weight: RAD-140 0.03–1 mg/kg/day → dose-dependent lean mass increase in castrated rats
Breast cancer research (AR+ PR- ER+ breast cancer)#
- RAD-140 mechanism in AR+ breast cancer: AR activation → suppresses ER transcription → anti-proliferative
- Phase 1b trial data: RAD-140 in AR+ advanced breast cancer → partial responses and stable disease in some patients
Neuroprotection#
- Unique among SARMs: RAD-140 shows neuroprotective activity in vitro and in vivo
- Protects hippocampal neurons from Aβ (amyloid-β) and kainic acid insult
- Mechanism: AR activation in neurons → downstream MAPK/ERK, PI3K/Akt neuroprotective pathways
- Relevant for Alzheimer's research models
Neuroprotective Effects#
RAD-140 neuroprotection has been documented in:
In vitro:
- Primary rat hippocampal neurons exposed to Aβ₁₋₄₂ oligomers: RAD-140 pretreatment (1–100 nM) → preserved cell viability, reduced caspase-3 activation
- Mechanism: AR → MAPK/ERK → CREB → neuroprotective gene expression (Bcl-2, BDNF)
- Testosterone has similar neuroprotection, but DHT does not → non-5α-reducible AR agonism required → RAD-140's non-steroidal structure
In vivo:
- Kainate excitotoxicity model in mice: RAD-140 SC → reduced hippocampal neuron loss, improved behavioral recovery (Morris water maze)
This neuroprotective profile is relevant for testosterone deficiency and neurodegenerative disease research.
HPTA Suppression Profile#
RAD-140, like all AR agonists, suppresses the HPTA:
- AR agonism at hypothalamus → GnRH suppression → LH/FSH fall
- BUT: no E2 production (RAD-140 does not aromatize) → only AR-mediated suppression (no estrogenic feedback component)
- At anabolic doses: LH/FSH suppressed ~50–80% in rats
- Testosterone: falls to castrate levels with sustained use (as with steroidal androgens)
- Recovery after cessation: faster than after steroidal androgens (shorter drug t½, no metabolite accumulation)
Research note: In intact male animal studies with RAD-140, include LH/FSH and testosterone measurements — endogenous testosterone suppression confounds interpretation of "RAD-140-specific" effects on any androgen-sensitive endpoint.
Research Protocols#
Hershberger assay: RAD-140 A:A ratio determination#
| Parameter | Specification |
|---|---|
| Model | Adult castrated male SD rats, 14-day post-castration recovery |
| Groups | 1. Vehicle, 2. TP reference 0.4 mg/kg/day SC × 10 days, 3–7. RAD-140: 0.01, 0.03, 0.1, 0.3, 1 mg/kg/day oral × 10 days |
| Endpoints | Levator ani mass (anabolic), ventral prostate mass (androgenic), seminal vesicle mass |
| Analysis | A:A ratio = levator ani dose-response / ventral prostate dose-response, both normalized to TP reference |
Neuroprotection: Aβ model#
| Parameter | Specification |
|---|---|
| Cell model | Primary rat hippocampal neurons (E18, day 7 in vitro) |
| Treatment | RAD-140 1–100 nM, pretreatment 30 min before Aβ₁₋₄₂ (5 µM, 24h) |
| Endpoints | Cell viability (MTT), LDH release (cytotoxicity), caspase-3 activity, MAPK/ERK phosphorylation (Western blot) |
| Specificity control | Flutamide (AR antagonist) co-treatment → confirms AR-mediated neuroprotection |
Key References#
-
Miller CP, et al. (2011). "Design, synthesis, and preclinical characterization of the selective androgen receptor modulator (SARM) RAD140." ACS Medicinal Chemistry Letters, 2(2):124–129.
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Jayaraman A, et al. (2014). "Selective androgen receptor modulator RAD140 is neuroprotective." Endocrinology, 155(12):4877–4886.
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Dalton JT. (2014). "Androgen receptor structure, function and biology." In: Principles of Andrology.
Research Use Only: RAD-140 is sold exclusively for in-vitro research and laboratory use. Not for unsupervised use. JuicedPharma does not provide medical advice.
Published by JuicedPharma Research Team · September 2026 · Category: Research Protocols & Science
