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| Other names | RAD140; RAD-140; EP0062; Testolone; Testalone |
| Routes of administration | By mouth[1][2] |
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| Eliminationhalf-life | 45–60 hours[2][3] |
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| Formula | C20H16ClN5O2 |
| Molar mass | 393.83 g·mol−1 |
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Vosilasarm, also known by the development codesRAD140 andEP0062 and by the black-market nameTestolone orTestalone, is aselective androgen receptor modulator (SARM) which is under development for the treatment ofhormone-sensitivebreast cancer.[4][5][6][7] It is specifically under development for the treatment ofandrogen receptor-positive,estrogen receptor-negative,HER2-negativeadvanced breast cancer.[4][5][8] Vosilasarm was also previously under development for the treatment ofsarcopenia (age-related muscle atrophy),osteoporosis, andweight loss due tocancer cachexia, but development for these indications was discontinued.[4][9] The drug is takenby mouth.[1][2]
Side effects of vosilasarm may includevomiting,dehydration,constipation,decreased appetite,weight loss, changes insex hormone levels,elevated liver enzymes, andliver toxicity.[2][10][11][12][13][14] Vosilasarm is anonsteroidal SARM, acting as anagonist of theandrogen receptor (AR), thebiological target ofandrogens andanabolic steroids liketestosterone anddihydrotestosterone (DHT).[15][7] However, it shows dissociation of effect between tissues inpreclinical studies, with agonistic andanabolic effects inmuscle, agonistic effects inbreast, andpartially agonistic orantagonistic effects in theprostate gland andseminal vesicles.[6][7][9][15][16]
Vosilasarm was developed in 2010 and was first described in the literature in 2011.[15][9] It was originally developed by Radius Health and is now under development by Ellipses Pharma.[4][5] The firstclinical study of vosilasarm, a small (n=22)phase 1 study in women withmetastatic breast cancer, was started in 2017 and completed in 2020, with results published in 2019, 2020, and 2022.[10][3][2][17][15] As of March 2023, vosilasarm is in phase 1/2clinical trials for the treatment of breast cancer.[4][18]
Aside from its development as a potentialpharmaceutical drug, vosilasarm is on theWorld Anti-Doping Agencylist of prohibited substances[19] and is sold forphysique- and performance-enhancing purposes by black-market Internet suppliers.[6][1] Vosilasarm is often used in these contexts at doses that have not been evaluated in clinical trials, with unknown effectiveness andsafety.[6][1] Many products sold online that are purported to be a specific SARM either contain none or contain other unrelated substances.[6][20]Social media has played an important role in facilitating the widespread non-medical use of SARMs.[21]
Vosilasarm is not approved for any medical use and is not available as a licensedpharmaceutical drug as of 2023.[4]
Side effects of vosilasarm in preliminary clinical studies in women with metastatic breast cancer have includedvomiting (27%),dehydration (27%),constipation,decreased appetite andweight loss (27%),hypophosphatemia, decreasedsex hormone-binding globulin (SHBG) levels (100%), increasedprostate-specific antigen (PSA) levels (80%), andabnormal liver function tests, including elevatedaspartate aminotransferase (59%), elevatedalanine aminotransferase (46%), and elevated total bloodbilirubin (27%).[2][10]
In gonadally intact malecynomolgus monkeys, vosilasarm suppressed testosterone levels by around 50% (from ~600–800 ng/dL to ~200–300 ng/dL) across three dose levels (0.01 mg/kg, 0.1 mg/kg, and 1.0 mg/kg).[6][9] Changes inserum lipids, including oftriglycerides,LDL cholesterol, andHDL cholesterol were also observed.[6][7][9]Elevated liver enzymes were minimally observed in monkeys.[6][7][9]
A number ofcase reports ofliver toxicity with non-medical use of vosilasarm have been published.[11][12][13][14] A case report of acutemyocarditis with non-medical use of vosilasarm also exists.[1][22]
Vosilasarm has been assessed in clinical trials in women with breast cancer at doses ranging from 50 to 150 mg/day, with the maximum safe and tolerated dose being 100 mg/day.[10][3][2] The drug sold via black-market Internet suppliers and used non-medically has been reported to be taken at doses of 5 to 30 mg/day, with unknown adverse effects and risks.[1][23]
Vosilasarm isselective androgen receptor modulator (SARM), or atissue-selective mixedagonist orpartial agonist of theandrogen receptor (AR).[6][7] This receptor is thebiological target ofendogenousandrogens liketestosterone anddihydrotestosterone (DHT) and ofsyntheticanabolic steroids likenandrolone andoxandrolone.[24][25][26][27] Vosilasarm shows highaffinity for the AR, with a Ki value of 7 nM (relative to 29 nM for testosterone and 10 nM for DHT).[6][7][9] It shows goodselectivity for the AR over othersteroid hormone receptors, with the closestoff-target receptor being theprogesterone receptor (IC50 = 750 nM versus 0.2 nM forprogesterone).[9] Vosilasarm also showspotentefficacy in terms of AR activation, with anEC50 value of 0.1 nM in theC2C12osteoblastdifferentiationassay.[7][9] The AR is widely expressed intissues throughout the body, including in theprostate gland,seminal vesicles,genitals,gonads,skin,hair follicles,muscle,bone,heart,adrenal cortex,liver,kidneys, andbrain, among others.[26][27] Vosilasarm has been found to have varyingfull agonist andpartial agonist AR-mediated effects in different tissues, includingpotent agonistic andanabolic activity inmuscle andbone, potent agonistic effects in AR-expressing humanbreast cancercell lines, and partial agonist or antagonist activity in theprostate gland andseminal vesicles.[6][7][9][15][16]
In castrated immature male rats, vosilasarm (at 10 mg/kg/day orally, the highest assessed dose) maximally stimulated prostate weight to 67%, seminal vesicle weight to 59%, andlevator ani muscle weight to 117% compared to that induced with testosterone propionate 1 mg/kg/day.[7][6][9] Moreover, when combined with testosterone propionate, vosilasarm partially antagonized the weight increases of the prostate gland and seminal vesicles, reducing them to 84% and 78% (both from 100%), respectively.[7][9] Conversely however, the combination of testosterone propionate and vosilasarm was additive in terms of levator ani muscle weight stimulation, increasing it to 124%.[7][9] Vosilasarm was found to stimulate muscle at a dose much lower than that required to stimulate the prostate.[7] A dose of 0.3 mg/kg/day stimulated levator ani muscle weight to a similar extent relative to the levator ani weight in non-castrated controls.[7][9] Conversely, a 33-fold higher dose of 10 mg/kg/day was required to stimulate prostate weight to a similar extent as that in non-castrated controls.[9] Similarly, in gonadally intact immature rats, 0.3 mg/kg/day vosilasarm stimulated levator ani muscle weight to a similar extent as testosterone propionate 0.5 mg/kg/day, but a dose of 30 mg/kg/day (100-fold higher) was required to stimulate the prostate to a similar extent as testosterone propionate 0.5 mg/kg/day.[7][6][9] Hence, in rats, vosilasarm is a potent full agonist of the levator ani muscle but a partial agonist and antagonist of the prostate and seminal vesicles, and is strongly selective for stimulating the levator ani muscle over the prostate gland.[7][9] In young male cynomolgus monkeys, vosilasarm, at oral doses of 0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day for 28 days,dose-dependently stimulatedbody weight (+10% at ≥0.1 mg/kg/day) and numerically increasedlean body mass.[7][6][15][9] The lack ofstatistical significance was likely due to the smallsample sizes per dosing group (n=3 each).[15][9] No data on vosilasarm and lean body mass in humans have been published as of 2022.[2][15]
Vosilasarm shows goodoralbioavailability in rats (27–63%) and monkeys (65–75%)[9] and isorally active in humans.[1][2] Theelimination half-life of vosilasarm is 45 to 60 hours.[2][3]
Vosilasarm is anoxadiazoleanilinederivative.[7] Other aniline SARMs includeAC-262536 andACP-105.[7]
Vosilasarm was developed by Radius Health in 2010.[15][9] It was first described in in the literature in 2011 in a paper detailing itsdesign,synthesis, andpreclinical characterizationin vitro and in rats and monkeys.[9] It was stated in this paper thatphase 1clinical studies of vosilasarm for treatment of severeweight loss due tocancer cachexia were being prepared.[9][7] However, these studies were never completed or published and development for this indication was discontinued.[4] Subsequently, vosilasarm was repurposed for the treatment ofbreast cancer.[4]
Vosilasarm is thegeneric name of the drug and itsInternational Nonproprietary Name (INN).[28] It is also known by its pharmaceutical developmental code names RAD140 (Radius Health) and EP0062 (Ellipses Pharma).[4] Additionally, vosilasarm is known by the black-market name Testolone or Testalone.[15][6][23]
Vosilasarm and other SARMs are sold by black-market vendors on the Internet.[6][20] Aside from vosilasarm, the other most commonly used SARMs includeenobosarm (ostarine; GTx-024, S-22),LGD-4033 (VK5211; "ligandrol"), andandarine (GTx-007; S-4).[21]Social media has played an important role in facilitating the widespread non-medical use of SARMs.[21]
The first-in-human study, aphase 1 trial, was initiated in October 2017 and completed in September 2020 inpostmenopausal women withbreast cancer.[10][3][2][17][15] The study investigated oral doses of vosilasarm of 50 mg/day to 150 mg/day, with the maximum tolerated dose found to be 100 mg/day.[10][3][2] A phase 1/2 study proposal of vosilasarm for treatment of breast cancer was published in 2023.[18] It will recruit up to 128 patients.[18]
