Ligandrol

Ligandrol
Clinical data
Other namesLGD4033; VK5211; VK-5211; Ligandrol; Anabolicum
Routes of
administration		By mouth[1][2]
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Elimination half-life24–36 hours[3][2][4]
Identifiers
  • 4-[(2R)-2-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H12F6N2O
Molar mass338.253 g·mol−1
3D model (JSmol)
  • FC([C@H](O)[C@H]1CCCN1C2=CC(=C(C#N)C=C2)C(F)(F)F)(F)F
  • InChI=1S/C14H12F6N2O/c15-13(16,17)10-6-9(4-3-8(10)7-21)22-5-1-2-11(22)12(23)14(18,19)20/h3-4,6,11-12,23H,1-2,5H2/t11-,12-/m1/s1
  • Key:OPSIVAKKLQRWKC-VXGBXAGGSA-N

LGD-4033, also known by the developmental code name VK5211 and by the black-market name Ligandrol, is a selective androgen receptor modulator (SARM) which is under development for the treatment of muscle atrophy in people with hip fracture.[5] It was also under development for the treatment of cachexia, hypogonadism, and osteoporosis, but development for these indications was discontinued.[5] LGD-4033 has been reported to dose-dependently improve lean body mass and muscle strength in preliminary clinical trials, but is still being developed and has not been approved for medical use.[5][6][7][8] The drug is taken by mouth.[1][2]

Known possible side effects of LGD-4033 include headache, dry mouth, adverse lipid changes like decreased high-density lipoprotein (HDL) cholesterol levels, changes in sex hormone concentrations like decreased testosterone levels, elevated liver enzymes, and liver toxicity.[9][1][10][3][2][11][6] The potential of LGD-4033 and other SARMs for producing masculinization is largely uncharacterized and hence is unknown.[3] LGD-4033 is a nonsteroidal SARM, acting as an agonist of the androgen receptor (AR), the biological target of androgens and anabolic steroids like testosterone and dihydrotestosterone (DHT).[10] However, it shows dissociation of effect between tissues in preclinical studies, with agonistic and anabolic effects in muscle and bone and partially agonistic or antagonistic effects in the prostate gland.[12][3][13]

LGD-4033 was first described in 2010.[12][4] It is less clinically studied than other SARMs like enobosarm, with only a few small clinical trials having been conducted and reported.[14][11][9][2][8] LGD-4033 has not yet completed clinical development or been approved for any use.[5][10][3] As of 2023, it is in phase 2 clinical trials for the treatment of hip fracture and muscle atrophy.[5] LGD-4033 was developed by Ligand Pharmaceuticals, and is now being developed by Viking Therapeutics.[5]

Aside from its development as a potential pharmaceutical drug, LGD-4033 is on the World Anti-Doping Agency list of prohibited substances[15] and is sold for physique- and performance-enhancing purposes by black-market Internet suppliers.[3][9] LGD-4033 is often used in these contexts at doses greatly exceeding those evaluated in clinical trials, with unknown effectiveness and safety.[3][9] Many products sold online that are purported to be LGD-4033 either contain none or contain other unrelated substances.[3][16] Social media has played an important role in facilitating the widespread non-medical use of SARMs.[17]

  1. ^ a b c Cite error: The named reference pmid26401842 was invoked but never defined (see the help page).
  2. ^ a b c d e Basaria S, Collins L, Dillon EL, Orwoll K, Storer TW, Miciek R, et al. (January 2013). "The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men". J Gerontol A Biol Sci Med Sci. 68 (1): 87–95. doi:10.1093/gerona/gls078. PMC 4111291. PMID 22459616.
  3. ^ a b c d e f g h Cite error: The named reference pmid33148520 was invoked but never defined (see the help page).
  4. ^ a b Cite error: The named reference MeglassonKapilLeibowitz2010 was invoked but never defined (see the help page).
  5. ^ a b c d e f "VK 5211 - AdisInsight".
  6. ^ a b Cite error: The named reference pmid36479151 was invoked but never defined (see the help page).
  7. ^ Girgis CM (2019). "Sex Steroid Hormones and Osteosarcopenia". Osteosarcopenia: Bone, Muscle and Fat Interactions. Cham: Springer International Publishing. pp. 173–190. doi:10.1007/978-3-030-25890-0_8. ISBN 978-3-030-25889-4. S2CID 209246318. Other molecules have been developed including LGD-4033 which increased muscle mass and strength in healthy males after 3 weeks (Basaria et al. 2013) [...] Recently, a phase 2 trial on the agent VK211 demonstrated dose-dependent increases in lean body mass, and improvements in physical performance in patients who had sustained hip fracture (Ristic et al. 2018). Whilst SARMs hold great promise as anabolic agents that may offer an effective therapy for osteosarcopenia, long-term side effects of these agents are unknown, studies are generally small and of short duration. Regulation of these products poses immense challenges with their high uptake on the black market and via the internet as performance-enhancing, body-building agents, which may overshadow their potential mainstream application in disorders of aging.
  8. ^ a b Cite error: The named reference RisticHarhajiSirbu2018 was invoked but never defined (see the help page).
  9. ^ a b c d Cite error: The named reference pmid37571268 was invoked but never defined (see the help page).
  10. ^ a b c Cite error: The named reference pmid32476495 was invoked but never defined (see the help page).
  11. ^ a b Cite error: The named reference pmid37218811 was invoked but never defined (see the help page).
  12. ^ a b Cite error: The named reference pmid23231475 was invoked but never defined (see the help page).
  13. ^ Cite error: The named reference VajdaMarschkevanOeveren2009 was invoked but never defined (see the help page).
  14. ^ "VK5211". Viking Therapeutics.
  15. ^ Cite error: The named reference WADA2014 was invoked but never defined (see the help page).
  16. ^ Van Wagoner RM, Eichner A, Bhasin S, Deuster PA, Eichner D (November 2017). "Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet". JAMA. 318 (20): 2004–2010. doi:10.1001/jama.2017.17069. PMC 5820696. PMID 29183075.
  17. ^ Hahamyan HA, Vasireddi N, Voos JE, Calcei JG (August 2023). "Social media's impact on widespread SARMs abuse". Phys Sportsmed. 51 (4): 291–293. doi:10.1080/00913847.2022.2078679. PMID 35574698.