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Purity: ≥98%
Testolone (formerly known as RAD140) is a novel, potent, nonsteroidal, orally bioavailable selective androgen receptor modulator (SARM) that is being researched for the treatment of diseases like breast cancer and muscle atrophy. Both male rats with kainate lesions and cultured neurons show neuroprotective effects from RAD140. RAD140 was found to be equally efficacious as testosterone in mitigating apoptotic insult-induced cell death in cultured hippocampal neurons. It was demonstrated that ERK phosphorylation was elevated and that the MAPK kinase inhibitor U0126 inhibited protection, indicating that RAD140 neuroprotection was mechanistically dependent upon MAPK signaling. Importantly, employing the rat kainate lesion model, RAD140 was also neuroprotective in vivo.
| Targets |
In a concentration-dependent manner, vosilasarm (0-300 nM; pretreated for 1 hour) increases neuron viability against Aβ[2].
In cultured neurons, vosilasarm (100 nM; 1 hour) guards against apoptotic insults. Vosilasarm exhibits protective profiles that considerably guard against Aβ and AAII-induced neuronal death, but not H2O2[2]. In neuronal cultures, votilasarm (100 nM; 15 minutes) significantly raises the levels of phosphorylated ERK, but not total ERK[2]. |
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| ln Vitro |
In a concentration-dependent manner, vosilasarm (0-300 nM; pretreated for 1 hour) increases neuron viability against Aβ[2].
In cultured neurons, vosilasarm (100 nM; 1 hour) guards against apoptotic insults. Vosilasarm exhibits protective profiles that considerably guard against Aβ and AAII-induced neuronal death, but not H2O2[2]. In neuronal cultures, votilasarm (100 nM; 15 minutes) significantly raises the levels of phosphorylated ERK, but not total ERK[2]. RAD140 demonstrated high affinity for the androgen receptor with a Ki of 7 nM, compared to testosterone (29 nM) and DHT (10 nM). It showed good selectivity over other steroid hormone nuclear receptors, with the closest off-target being the progesterone receptor (IC50 = 750 nM). In the C2C12 osteoblast differentiation assay, RAD140 exhibited functional androgen agonist activity with an EC50 of 0.1 nM (DHT = 0.05 nM). [1] |
| ln Vivo |
Vosilasarm exhibits good bioavailability in rats (F = 27-63%) and monkeys (65-75%), as well as high stability (t1/2 > 2 h) in incubations with rat, monkey, and human microsomes[1].
Vosilasarm (0.03-0.3 mg/kg; for 11 days) increases the weight of the prostate and the levator ani bulbocavernosus muscle in immature castrated rats[1]. The effect of testosterone propionate (TP) at 1 mg/kg on seminal vesicles is actually countered by a high dose of Vosilasarm (10 mg/kg, p.o. ), but TP's effect on the levator ani muscle is enhanced. Vosilasarm can induce antagonism at an effective dose of 0.3–1 mg/kg (p.o.) for 1 mg/kg TP (s.c.). Vosilasarm appears to be a strong and complete androgen agonist on the levator ani, but a weaker, partial antagonist on the seminal vesicle and potentially the prostate in the young castrate male rat model[1]. Vosilasarm is shown to be neuroprotective in vivo in the rat kainate lesion model. Vosilasarm has been shown in studies involving gonadectomized adult male rats to exhibit peripheral tissue-specific androgen action that largely spared prostate, neural efficacy as evidenced by activation of androgenic gene regulation effects, and neuroprotection of hippocampal neurons against cell death caused by systemic administration of the excitotoxin kainate[2]. In young castrated male rats, RAD140 stimulated levator ani muscle weight starting at 0.03 mg/kg (po) and reached sham-operated animal levels at 0.3 mg/kg, while showing minimal stimulation of prostate and seminal vesicles. In young intact male rats, RAD140 increased levator ani muscle weight starting at 0.1 mg/kg (po) but did not stimulate prostate weight until 30 mg/kg. In cynomolgus monkeys, RAD140 administered at 0.1 mg/kg (po) for 28 days resulted in >10% body weight gain, with lean mass increase observed via DEXA scan. Co-administration of RAD140 (10 mg/kg, po) with testosterone propionate (1 mg/kg, sc) antagonized TP-induced seminal vesicle stimulation but enhanced TP-induced levator ani muscle stimulation. [1] |
| Enzyme Assay |
AR binding assay was performed using a fluorometric assay with a fluorescent-tagged AR-ligand methyltrienolone (R1881) as tracer. Ki values were derived using the Cheng–Prusoff equation with Kd set to 25 nM for R1881. [1]
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| Cell Assay |
C2C12 osteoblast differentiation assay was used to assess functional androgen agonist activity. The procedure involved measuring osteoblast differentiation in response to compound treatment, with EC50 calculated from dose-response curves. [1]
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| Animal Protocol |
Young castrated male rats were treated with RAD140 orally in 0.5% methylcellulose for 11 days. Testosterone propionate (TP) was administered subcutaneously in corn oil at 1 mg/kg as a comparator.
Young intact male rats were treated orally with RAD140 in 0.5% methylcellulose for 11 days. Cynomolgus monkeys were dosed orally with RAD140 at 0.01, 0.1, and 1 mg/kg for 28 days, with body weight and DEXA scans performed pre- and post-dosing. For antagonism studies, rats were co-administered RAD140 (10 mg/kg, po) and TP (1 mg/kg, sc). [1] |
| ADME/Pharmacokinetics |
RAD140 showed high stability in rat, monkey, and human microsomes (t1/2 > 2 hours). Oral bioavailability in rats was 27–65%, and in monkeys it was 65–75%. In rats, exposure increased linearly with dose up to 10 mg/kg (orally). In monkeys, exposure increased with dose throughout the study period. [1]
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| Toxicity/Toxicokinetics |
In monkeys, no increase in liver transaminase levels more than twice the baseline was observed regardless of the dose, including doses more than 10 times the fully effective dose. As expected, androgen treatment reduced lipid levels (low-density lipoprotein, high-density lipoprotein, triglycerides). Even at doses as low as 0.01 mg/kg, testosterone levels were suppressed in monkeys after 28 days of administration. [1]
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| References |
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| Additional Infomation |
RAD140 is an investigational selective androgen receptor modulator (SARM) for the treatment of conditions such as muscle atrophy and breast cancer. Vosilasarm is a highly bioavailable, orally administered nonsteroidal selective androgen receptor modulator (SARM) with potential tissue-selective androgenic/anti-androgenic activity. After oral administration, Vosilasarm acts as an agonist in specific tissues, such as skeletal muscle and bone, binding to and activating androgen receptors (ARs). In the prostate and breast, Vosilasarm acts as an antagonist, blocking AR activation and AR-mediated cell proliferation. Therefore, this drug may improve bone formation, increase muscle mass and strength, and may inhibit prostate growth in men and the proliferation of AR-dependent breast cancer cells. Selective androgen receptor modulators (SARMs) have lower androgenic activity compared to anabolic agents. RAD140 is a potent, orally bioavailable, nonsteroidal selective androgen receptor modulator (SARM) designed to stimulate muscle and bone growth while minimizing effects on sex tissues. It acts as a full agonist on muscles (levator ani), but as a partial antagonist on the seminal vesicles, and may also affect the prostate in the presence of testosterone. It is being developed for the treatment of cancer cachexia patients, and preclinical toxicology studies in rats and monkeys have been completed, with plans to conduct Phase I clinical trials. [1]
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| Molecular Formula |
C20H16CLN5O2
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| Molecular Weight |
393.83
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| Exact Mass |
393.099
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| Elemental Analysis |
C, 61.00; H, 4.10; Cl, 9.00; N, 17.78; O, 8.12
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| CAS # |
1182367-47-0
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| Related CAS # |
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| PubChem CID |
44200882
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
687.7±65.0 °C at 760 mmHg
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| Flash Point |
369.7±34.3 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.652
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| LogP |
3.02
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
623
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1=C(C)C(N[C@]([H])([C@@]([H])(O)C)C2=NN=C(O2)C3=CC=C(C#N)C=C3)=CC=C1C#N
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| InChi Key |
XMBUPPIEVAFYHO-KPZWWZAWSA-N
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| InChi Code |
InChI=1S/C20H16ClN5O2/c1-11-16(8-7-15(10-23)17(11)21)24-18(12(2)27)20-26-25-19(28-20)14-5-3-13(9-22)4-6-14/h3-8,12,18,24,27H,1-2H3/t12-,18+/m0/s1
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| Chemical Name |
2-chloro-4-[[(1R,2S)-1-[5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl]-2-hydroxypropyl]amino]-3-methylbenzonitrile
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.35 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5392 mL | 12.6958 mL | 25.3917 mL | |
| 5 mM | 0.5078 mL | 2.5392 mL | 5.0783 mL | |
| 10 mM | 0.2539 mL | 1.2696 mL | 2.5392 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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Tissue-selective antagonist activity ofRAD140.ACS Med Chem Lett.2010 Dec 2;2(2):124-9. |
Tissue-selective agonist activity ofRAD140in young intact male rats.ACS Med Chem Lett.2010 Dec 2;2(2):124-9. |
Primate body weight from day −21, through 28 days dosing and 21 days postdosing withRAD140(0.01, 0.1, and 1 mg/kg, po).ACS Med Chem Lett.2010 Dec 2;2(2):124-9. |
RAD140 is neuroprotective against apoptotic insults.Endocrinology.2014 Apr;155(4):1398-406. |
RAD140 induces tissue-specific androgenic effects.Endocrinology.2014 Apr;155(4):1398-406. |
Quantitative analyses of MAPK signaling in SARM neuroprotection.Endocrinology.2014 Apr;155(4):1398-406. |
RAD140 reduces neuronal cell death cause by kainate.
RAD140 increases neuron viability against Aβ in a concentration-dependent manner.Endocrinology.2014 Apr;155(4):1398-406. |
Kainate-induced seizures are not affected by androgen status Behavioral features of kainate-induced seizures were monitored and quantified for a 3-hour period following the lesion.Endocrinology.2014 Apr;155(4):1398-406. |
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