WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 531875
CAS#: 1216744-19-2
Description: GSK4112 is a selective Rev-Erbα agonist (EC50 = 250 nM). GSK4112 enhances recruitment of nuclear receptor co-repressor (NCoR) peptide to Rev-Erbα and causes acute suppression of Bmal1 gene transcription.
MedKoo Cat#: 531875
Name: GSK4112
CAS#: 1216744-19-2
Chemical Formula: C18H21ClN2O4S
Exact Mass: 396.0911
Molecular Weight: 396.886
Elemental Analysis: C, 54.47; H, 5.33; Cl, 8.93; N, 7.06; O, 16.12; S, 8.08
Synonym: GSK4112; GSK 4112; GSK-4112.
IUPAC/Chemical Name: tert-butyl 2-[(4-chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]acetate
InChi Key: WYSLOKHVFKLWOU-UHFFFAOYSA-N
InChi Code: InChI=1S/C18H21ClN2O4S/c1-18(2,3)25-17(22)12-20(10-13-4-6-14(19)7-5-13)11-15-8-9-16(26-15)21(23)24/h4-9H,10-12H2,1-3H3
SMILES Code: O=C(OC(C)(C)C)CN(CC1=CC=C(Cl)C=C1)CC2=CC=C([N+]([O-])=O)S2
Appearance: Solid powder
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: | GSK4112 (SR6452) is a Rev-erbα agonist with an EC50 value of 0.4 μM. |
| In vitro activity: | Human fetal lung fibroblast 1 (HFL-1) cells were treated with TGF-β with or without GSK4112 (REV-ERBα agonist) for 3 days (Figure 11A). The TGF-β–induced increase in gene expression of ACTA2 (αSMA) was significantly inhibited by GSK4112 treatment in HFL-1 cells, whereas mRNA levels of COL1A1 and FN1 (fibronectin) were reduced by GSK4112 but not significantly. Reference: JCI Insight. 2021 Jun 22;6(12):e145200. https://pubmed.ncbi.nlm.nih.gov/34014841/ |
| In vivo activity: | Consistent with the histological abnormalities, the plasma ALT and AST increased significantly following Jo2 exposure, whereas treatment with GSK4112 suppressed the increase of ALT and AST in Jo2-exposed mice (Fig. 2). In addition, treatment with GSK4112 markedly improved the survival rate of Jo2-exposed mice (Fig. 3). Reference: Int J Med Sci. 2021 Oct 25;18(16):3831-3838. https://pubmed.ncbi.nlm.nih.gov/34790059/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 3.0 | 7.56 | |
| DMSO | 28.23 | 71.13 | |
| Ethanol | 2.0 | 5.04 |
The following data is based on the product molecular weight 396.886 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. Wang Q, Sundar IK, Lucas JH, Muthumalage T, Rahman I. Molecular clock REV-ERBα regulates cigarette smoke-induced pulmonary inflammation and epithelial-mesenchymal transition. JCI Insight. 2021 Jun 22;6(12):e145200. doi: 10.1172/jci.insight.145200. PMID: 34014841; PMCID: PMC8262497. 2. Tao L, Yu H, Liang R, Jia R, Wang J, Jiang K, Wang Z. Rev-erbα inhibits proliferation by reducing glycolytic flux and pentose phosphate pathway in human gastric cancer cells. Oncogenesis. 2019 Oct 7;8(10):57. doi: 10.1038/s41389-019-0168-5. PMID: 31591390; PMCID: PMC6779746. 3. Shao R, Yang Y, Fan K, Wu X, Jiang R, Tang L, Li L, Shen Y, Liu G, Zhang L. REV-ERBα Agonist GSK4112 attenuates Fas-induced Acute Hepatic Damage in Mice. Int J Med Sci. 2021 Oct 25;18(16):3831-3838. doi: 10.7150/ijms.52011. PMID: 34790059; PMCID: PMC8579287. 4. Kim K, Kim JH, Kim I, Seong S, Kim N. Rev-erbα Negatively Regulates Osteoclast and Osteoblast Differentiation through p38 MAPK Signaling Pathway. Mol Cells. 2020 Jan 31;43(1):34-47. doi: 10.14348/molcells.2019.0232. PMID: 31896234; PMCID: PMC6999712. |
| In vitro protocol: | 1. Wang Q, Sundar IK, Lucas JH, Muthumalage T, Rahman I. Molecular clock REV-ERBα regulates cigarette smoke-induced pulmonary inflammation and epithelial-mesenchymal transition. JCI Insight. 2021 Jun 22;6(12):e145200. doi: 10.1172/jci.insight.145200. PMID: 34014841; PMCID: PMC8262497. 2. Tao L, Yu H, Liang R, Jia R, Wang J, Jiang K, Wang Z. Rev-erbα inhibits proliferation by reducing glycolytic flux and pentose phosphate pathway in human gastric cancer cells. Oncogenesis. 2019 Oct 7;8(10):57. doi: 10.1038/s41389-019-0168-5. PMID: 31591390; PMCID: PMC6779746. |
| In vivo protocol: | 1. Shao R, Yang Y, Fan K, Wu X, Jiang R, Tang L, Li L, Shen Y, Liu G, Zhang L. REV-ERBα Agonist GSK4112 attenuates Fas-induced Acute Hepatic Damage in Mice. Int J Med Sci. 2021 Oct 25;18(16):3831-3838. doi: 10.7150/ijms.52011. PMID: 34790059; PMCID: PMC8579287. 2. Kim K, Kim JH, Kim I, Seong S, Kim N. Rev-erbα Negatively Regulates Osteoclast and Osteoblast Differentiation through p38 MAPK Signaling Pathway. Mol Cells. 2020 Jan 31;43(1):34-47. doi: 10.14348/molcells.2019.0232. PMID: 31896234; PMCID: PMC6999712. |
1: Chen H, Chu G, Zhao L, Yamauchi N, Shigeyoshi Y, Hashimoto S, Hattori MA. Rev-erbα regulates circadian rhythms and StAR expression in rat granulosa cells as identified by the agonist GSK4112. Biochem Biophys Res Commun. 2012 Apr 6;420(2):374-9. doi: 10.1016/j.bbrc.2012.02.164. PubMed PMID: 22425774.
2: Grant D, Yin L, Collins JL, Parks DJ, Orband-Miller LA, Wisely GB, Joshi S, Lazar MA, Willson TM, Zuercher WJ. GSK4112, a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erbα. ACS Chem Biol. 2010 Oct 15;5(10):925-32. doi: 10.1021/cb100141y. PubMed PMID: 20677822.
