RAD-140

Overview

RAD-140 (testolone) is a non-steroidal small-molecule selective androgen receptor modulator (SARM) — not a peptide — developed by Radius Health. It is NOT FDA-approved for any indication. Grey-market use for bodybuilding is associated with documented drug-induced liver injury (hepatotoxicity), testosterone suppression, and adverse cardiovascular effects. It is a WADA-prohibited substance. It is tracked in peptide-research spaces because of overlapping grey-market performance use.

Mechanism of Action

RAD-140 binds the androgen receptor with high affinity and acts as a tissue-selective AR agonist — anabolic in skeletal muscle and bone with relatively reduced androgenic activity in prostate and sebaceous glands in preclinical models. Selectivity is dose-dependent and modest, and RAD-140 still suppresses the HPG axis via negative feedback, reducing endogenous testosterone. It does not aromatize to estrogen.

Research Summary

Miller et al. (2010, ACS Med Chem Lett) first described the design, synthesis, and preclinical characterization of RAD140 as a high-affinity tissue-selective AR agonist. Jayaraman et al. (2014, Endocrinology) demonstrated neuroprotection in cultured neurons and kainate-lesioned rats. LoRusso et al. (2022, Clinical Breast Cancer) reported the first-in-human Phase 1 dose-escalation in ER+/HER2- metastatic breast cancer (MTD 100 mg/day); efficacy was modest and hepatic AEs were frequent (AST 59%, ALT 46%, bilirubin 27%), and development did not progress to approval. Leung et al. (2022, Ochsner Journal) and subsequent case series document severe cholestatic drug-induced liver injury from grey-market RAD-140 use. Van Wagoner et al. (2017, JAMA) showed that only ~52% of internet-marketed SARM products contained the labeled compound, compounding grey-market risk. FDA has issued public warnings that SARMs are not safe for human consumption, and RAD-140 is banned by WADA. No FDA approval pathway is currently established.

Reported Side Effects

• Drug-induced liver injury / hepatotoxicity (multiple published case reports, including cholestatic hepatitis with markedly elevated bilirubin)
• Testosterone / HPG axis suppression (dose-dependent, commonly requires PCT in grey-market use)
• HDL cholesterol suppression and potential cardiovascular risk
• Elevated AST/ALT and total bilirubin
• Hair shedding
• Headache
• Aggression or mood changes
• Acne

Compare RAD-140 with Others

Research References

• Design, Synthesis, and Preclinical Characterization of the Selective Androgen Receptor Modulator (SARM) RAD140 (Miller et al., ACS Med Chem Lett) (2010)
• Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats (Jayaraman et al., Endocrinology) (2014)
• A First-in-Human Phase 1 Study of a Novel Selective Androgen Receptor Modulator (SARM), RAD140, in ER+/HER2- Metastatic Breast Cancer (LoRusso et al., Clinical Breast Cancer) (2022)
• RAD-140 Drug-Induced Liver Injury (Leung et al., Ochsner Journal) — cholestatic hepatitis case report (2022)
• Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet (Van Wagoner et al., JAMA) (2017)

Frequently asked questions

How does RAD-140 work?

RAD-140 binds the androgen receptor with high affinity and acts as a tissue-selective AR agonist — anabolic in skeletal muscle and bone with relatively reduced androgenic activity in prostate and sebaceous glands in preclinical models. Selectivity is dose-dependent and modest, and RAD-140 still suppresses the HPG axis via negative feedback, reducing endogenous testosterone. It does not aromatize to estrogen.

What does the research say about RAD-140?

Miller et al. (2010, ACS Med Chem Lett) first described the design, synthesis, and preclinical characterization of RAD140 as a high-affinity tissue-selective AR agonist. Jayaraman et al. (2014, Endocrinology) demonstrated neuroprotection in cultured neurons and kainate-lesioned rats. LoRusso et al. (2022, Clinical Breast Cancer) reported the first-in-human Phase 1 dose-escalation in ER+/HER2- metastatic breast cancer (MTD 100 mg/day); efficacy was modest and hepatic AEs were frequent (AST 59%, ALT 46%, bilirubin 27%), and development did not progress to approval. Leung et al. (2022, Ochsner Journal) and subsequent case series document severe cholestatic drug-induced liver injury from grey-market RAD-140 use. Van Wagoner et al. (2017, JAMA) showed that only ~52% of internet-marketed SARM products contained the labeled compound, compounding grey-market risk. FDA has issued public warnings that SARMs are not safe for human consumption, and RAD-140 is banned by WADA. No FDA approval pathway is currently established.