GSK-2881078 Research Standard
GSK-2881078 (CAS 1539314-06-1) is a nonsteroidal androgen receptor ligand of the indole structural class, supplied as a reference standard for androgen receptor pharmacology and analytical method development. Its structural class matters for method work: SARM screening panels are organised by chemical class, and the indole SARMs sit apart from the arylpropionamides, quinolinones and phenyl-oxadiazoles.[3]
Mechanism of Action & Research Context
The molecular target is the androgen receptor (AR, NR3C4), a ligand-activated nuclear hormone receptor that functions as a transcription factor.
An indole-class AR ligand. The scaffold is distinct from the arylpropionamide (andarine, ostarine, S-23), quinolinone (LGD-2226, LGD-3303), pyrrolidinyl-benzonitrile (LGD-4033) and phenyl-oxadiazole (RAD-140) series, and is catalogued as its own class in validated screening methods.[3]
Characterised phase I metabolism. Three metabolites have been identified in equine liver microsomes, reported there for the first time.[1]
An analytical outlier worth knowing. In a validated urine screening method covering 19 SARMs, detection capability fell in the 0.1–1.0 ng/mL range for the panel — with GSK2881078 explicitly excepted. Its detection behaviour differs from the rest of the panel, which matters when designing a method meant to cover it.[3]
Distinct genomic and non-genomic routes. Nonsteroidal SARMs and endogenous androgens engage AR through different signalling arms and assemble different AR/cofactor complexes at androgen-responsive enhancers, so the two ligand types are not interchangeable in mechanistic work.[4]
Coregulator recruitment and dimerisation. A SARM can drive AR transcriptional activity while producing markedly less AR homodimerisation than DHT and recruiting only a restricted subset of cofactors, with p160 coactivators SRC1, TIF2 and NCoA3 notably absent in yeast two-hybrid assays. Differential coregulator recruitment is the leading mechanistic account of tissue selectivity.[5]
Research Applications
Primary fields of in vitro and preclinical laboratory investigation include:
AR binding and transactivation assays with nuclear-receptor counter-screens.[4,5]
Metabolite identification in liver microsome incubations.[1]
Cross-class analytical method development, where an indole-class standard is needed alongside arylpropionamides and quinolinones.[2,3]
Analytical Documentation
Purity and identity vary by manufacturing lot. Kimera Chems does not publish a single fixed purity figure for this item; refer to the batch-specific Certificate of Analysis (COA) issued for the lot received, which reflects third-party analytical testing for that lot.
References
- Cutler C, Viljanto M, Taylor P, Hincks P, Biddle S, Van Eenoo P. Identification of equine in vitro metabolites of seven non-steroidal selective androgen receptor modulators for doping control purposes. Drug Test Anal. 2022;14(2):349–370. doi:10.1002/dta.3189
- Ventura E, Gadaj A, Buckley T, Mooney MH. Development of a multi-residue high-throughput UHPLC-MS/MS method for routine monitoring of SARM compounds in equine and bovine blood. Drug Test Anal. 2020;12(9):1373–1379. doi:10.1002/dta.2875
- Stacchini C, Botrè F, Comunità F, et al. Simultaneous detection of different chemical classes of selective androgen receptor modulators in urine by liquid chromatography-mass spectrometry-based techniques. J Pharm Biomed Anal. 2021;195:113849. doi:10.1016/j.jpba.2020.113849
- Narayanan R, Coss CC, Yepuru M, et al. Steroidal androgens and nonsteroidal, tissue-selective androgen receptor modulator, S-22, regulate androgen receptor function through distinct genomic and nongenomic signaling pathways. Mol Endocrinol. 2008;22(11):2448–2465. doi:10.1210/me.2008-0160
- Furuya K, Yamamoto N, Ohyabu Y, et al. Mechanism of the tissue-specific action of the selective androgen receptor modulator S-101479. Biol Pharm Bull. 2013;36(3):442–451. doi:10.1248/bpb.b12-00885
Storage & Handling
Store at controlled room temperature. Keep tightly closed. Liquid formats: do not refrigerate or freeze. Cold storage may cause the solution to cloud or precipitate. If this occurs, return to room temperature and mix until clear.
Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.
