Synonym
GLPG-0492; GLPG 0492; GLPG0492;
IUPAC/Chemical Name
(S)-4-(4-(hydroxymethyl)-3-methyl-2,5-dioxo-4-phenylimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile
InChi Key
VAJGULUVTFDTAS-GOSISDBHSA-N
InChi Code
InChI=1S/C19H14F3N3O3/c1-24-17(28)25(14-8-7-12(10-23)15(9-14)19(20,21)22)16(27)18(24,11-26)13-5-3-2-4-6-13/h2-9,26H,11H2,1H3/t18-/m1/s1
SMILES Code
N#CC1=CC=C(N(C(N(C)[C@]2(CO)C3=CC=CC=C3)=O)C2=O)C=C1C(F)(F)F
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
GLPG0492 is a non-steroidal selective androgen receptor modulator (potency 12 nM).
In vitro activity:
Molecular modeling of the binding to the androgen receptor ligand binding domain suggests slight differences in the binding modes of RAD-140, GSK-2881078 and GLPG0492. In conclusion, androgenic activity of the three non-steroidal compounds in the two different in vitro test systems confirmed the results of the in silico modeling of the androgen receptor binding.
Reference: J Steroid Biochem Mol Biol. 2019 May;189:81-86. https://pubmed.ncbi.nlm.nih.gov/30825507/
In vivo activity:
Sciatic nerve blood flow (SNBF) was markedly lower (about 43.4%) in untreated diabetic (DC) rats than in non-diabetic controls (NC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol and fructose values were observed in the sciatic nerve, accompanied by a markedly higher sorbitol concentration in erythrocytes. In contrast, TAT-treated diabetic groups (DT-10, DT-40 and DT-200) had significantly higher SNBF, MNCV and sciatic nerve myo-inositol values and lower sciatic nerve sorbitol and fructose levels and erythrocyte sorbitol concentration than the DC group.
Reference: Diabetes Res Clin Pract. 1995 Feb;27(2):107-17. https://pubmed.ncbi.nlm.nih.gov/7607048/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
50.0 |
128.42 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
389.33
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Zierau O, Kolodziejczyk A, Vollmer G, Machalz D, Wolber G, Thieme D, Keiler AM. Comparison of the three SARMs RAD-140, GLPG0492 and GSK-2881078 in two different in vitro bioassays, and in an in silico androgen receptor binding assay. J Steroid Biochem Mol Biol. 2019 May;189:81-86. doi: 10.1016/j.jsbmb.2019.02.014. Epub 2019 Feb 27. PMID: 30825507.
2. Nique F, Hebbe S, Triballeau N, Peixoto C, Lefrançois JM, Jary H, Alvey L, Manioc M, Housseman C, Klaassen H, Van Beeck K, Guédin D, Namour F, Minet D, Van der Aar E, Feyen J, Fletcher S, Blanqué R, Robin-Jagerschmidt C, Deprez P. Identification of a 4-(hydroxymethyl)diarylhydantoin as a selective androgen receptor modulator. J Med Chem. 2012 Oct 11;55(19):8236-47. doi: 10.1021/jm300281x. Epub 2012 Sep 25. PMID: 22957947.
3. Hotta N, Kakuta H, Fukasawa H, Koh N, Sakakibara F, Nakamura J, Hamada Y, Wakao T, Hara T, Mori K, et al. Effect of a potent new aldose reductase inhibitor, (5-(3-thienyltetrazol-1-yl)acetic acid (TAT), on diabetic neuropathy in rats. Diabetes Res Clin Pract. 1995 Feb;27(2):107-17. doi: 10.1016/0168-8227(95)01033-a. PMID: 7607048.
In vitro protocol:
1. Zierau O, Kolodziejczyk A, Vollmer G, Machalz D, Wolber G, Thieme D, Keiler AM. Comparison of the three SARMs RAD-140, GLPG0492 and GSK-2881078 in two different in vitro bioassays, and in an in silico androgen receptor binding assay. J Steroid Biochem Mol Biol. 2019 May;189:81-86. doi: 10.1016/j.jsbmb.2019.02.014. Epub 2019 Feb 27. PMID: 30825507.
In vivo protocol:
1. Nique F, Hebbe S, Triballeau N, Peixoto C, Lefrançois JM, Jary H, Alvey L, Manioc M, Housseman C, Klaassen H, Van Beeck K, Guédin D, Namour F, Minet D, Van der Aar E, Feyen J, Fletcher S, Blanqué R, Robin-Jagerschmidt C, Deprez P. Identification of a 4-(hydroxymethyl)diarylhydantoin as a selective androgen receptor modulator. J Med Chem. 2012 Oct 11;55(19):8236-47. doi: 10.1021/jm300281x. Epub 2012 Sep 25. PMID: 22957947.
2. Hotta N, Kakuta H, Fukasawa H, Koh N, Sakakibara F, Nakamura J, Hamada Y, Wakao T, Hara T, Mori K, et al. Effect of a potent new aldose reductase inhibitor, (5-(3-thienyltetrazol-1-yl)acetic acid (TAT), on diabetic neuropathy in rats. Diabetes Res Clin Pract. 1995 Feb;27(2):107-17. doi: 10.1016/0168-8227(95)01033-a. PMID: 7607048.
1: Blanqué R, Lepescheux L, Auberval M, Minet D, Merciris D, Cottereaux C, Clément-Lacroix P, Delerive P, Namour F. Characterization of GLPG0492, a selective androgen receptor modulator, in a mouse model of hindlimb immobilization. BMC Musculoskelet Disord. 2014 Sep 3;15:291. doi: 10.1186/1471-2474-15-291. PubMed PMID: 25185887; PubMed Central PMCID: PMC4167280.
2: Cozzoli A, Capogrosso RF, Sblendorio VT, Dinardo MM, Jagerschmidt C, Namour F, Camerino GM, De Luca A. GLPG0492, a novel selective androgen receptor modulator, improves muscle performance in the exercised-mdx mouse model of muscular dystrophy. Pharmacol Res. 2013 Jun;72:9-24. doi: 10.1016/j.phrs.2013.03.003. PubMed PMID: 23523664.
3: Nique F, Hebbe S, Triballeau N, Peixoto C, Lefrançois JM, Jary H, Alvey L, Manioc M, Housseman C, Klaassen H, Van Beeck K, Guédin D, Namour F, Minet D, Van der Aar E, Feyen J, Fletcher S, Blanqué R, Robin-Jagerschmidt C, Deprez P. Identification of a 4-(hydroxymethyl)diarylhydantoin as a selective androgen receptor modulator. J Med Chem. 2012 Oct 11;55(19):8236-47. doi: 10.1021/jm300281x. PubMed PMID: 22957947.
4: Thevis M, Schänzer W. Detection of SARMs in doping control analysis. Mol Cell Endocrinol. 2017 Jan 27. pii: S0303-7207(17)30053-9. doi: 10.1016/j.mce.2017.01.040. [Epub ahead of print] PubMed PMID: 28137616.
