GSK-2881078

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

1. 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
2. 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
3. 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
4. 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
5. 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.

Related Research Compounds

• LGD-2226
• OTR-AC
• MID-35
• ACE-031

Research Use Only Disclaimer: This product is labeled and sold "For Research Use Only - NOT FOR HUMAN CONSUMPTION." It is not a drug, dietary supplement, food, cosmetic, or medical device, and it is not approved by the FDA or any other regulator for human or veterinary use. It is supplied to approved account holders as a research chemical for laboratory use and must be handled in accordance with applicable law.