GSK-4112

GSK-4112
Identifiers
	IUPAC name tert-butyl 2-[(4-chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]acetate;
CAS Number	1216744-19-2;
PubChem CID	50905018;
ChemSpider	24606038;
ChEMBL	ChEMBL1961795;
CompTox Dashboard (EPA)	DTXSID701336675 ;
Chemical and physical data
Formula	C18H21ClN2O4S
Molar mass	396.89 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)(C)OC(=O)CN(CC1=CC=C(C=C1)Cl)CC2=CC=C(S2)[N+](=O)[O-];
	InChI 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; Key:WYSLOKHVFKLWOU-UHFFFAOYSA-N;

GSK-4112 is an experimental drug that was developed by GlaxoSmithKline as an agonist of Rev-ErbAα.^[1] It is used for studying regulation of the circadian rhythm and its influence on diverse processes such as adipogenesis,^[2]^[3] regulation of bone density,^[4] and inflammation.^[5]^[6]^[7]^[8]

References

^ Grant D, Yin L, Collins JL, Parks DJ, Orband-Miller LA, Wisely GB, et al. (October 2010). "GSK4112, a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erbα". ACS Chemical Biology. 5 (10): 925–32. doi:10.1021/cb100141y. PMID 20677822.
^ Kojetin DJ, Burris TP (2011). "A role for rev-erbα ligands in regulation of adipogenesis". Current Pharmaceutical Design. 17 (4): 320–4. doi:10.2174/138161211795164211. PMID 21375499.
^ Chu G, Zhou X, Hu Y, Shi S, Yang G (September 2019). "Rev-erbα Inhibits Proliferation and Promotes Apoptosis of Preadipocytes through the Agonist GSK4112". International Journal of Molecular Sciences. 20 (18): 4524. doi:10.3390/ijms20184524. PMC 6769707. PMID 31547330.
^ Kim K, Kim JH, Kim I, Seong S, Kim N (January 2020). "Rev-erbα Negatively Regulates Osteoclast and Osteoblast Differentiation through p38 MAPK Signaling Pathway". Molecules and Cells. 43 (1): 34–47. doi:10.14348/molcells.2019.0232. PMC 6999712. PMID 31896234.
^ Sato S, Sakurai T, Ogasawara J, Takahashi M, Izawa T, Imaizumi K, et al. (January 2014). "A circadian clock gene, Rev-erbα, modulates the inflammatory function of macrophages through the negative regulation of Ccl2 expression". Journal of Immunology. 192 (1): 407–17. doi:10.4049/jimmunol.1301982. PMID 24307731.
^ Sundar IK, Rashid K, Sellix MT, Rahman I (December 2017). "The nuclear receptor and clock gene REV-ERBα regulates cigarette smoke-induced lung inflammation". Biochemical and Biophysical Research Communications. 493 (4): 1390–1395. doi:10.1016/j.bbrc.2017.09.157. PMC 5756581. PMID 28974420.
^ Guo DK, Zhu Y, Sun HY, Xu XY, Zhang S, Hao ZB, et al. (January 2019). "Pharmacological activation of REV-ERBα represses LPS-induced microglial activation through the NF-κB pathway". Acta Pharmacologica Sinica. 40 (1): 26–34. doi:10.1038/s41401-018-0064-0. PMC 6318300. PMID 29950615.
^ Morioka N, Kodama K, Tomori M, Yoshikawa K, Saeki M, Nakamura Y, et al. (May 2019). "Stimulation of nuclear receptor REV-ERBs suppresses production of pronociceptive molecules in cultured spinal astrocytes and ameliorates mechanical hypersensitivity of inflammatory and neuropathic pain of mice" (PDF). Brain, Behavior, and Immunity. 78: 116–130. doi:10.1016/j.bbi.2019.01.014. PMID 30682503. S2CID 59273997.

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[1] Grant D, Yin L, Collins JL, Parks DJ, Orband-Miller LA, Wisely GB, et al. (October 2010). "GSK4112, a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erbα". ACS Chemical Biology. 5 (10): 925–32. doi:10.1021/cb100141y. PMID 20677822.

[2] Kojetin DJ, Burris TP (2011). "A role for rev-erbα ligands in regulation of adipogenesis". Current Pharmaceutical Design. 17 (4): 320–4. doi:10.2174/138161211795164211. PMID 21375499.

[3] Chu G, Zhou X, Hu Y, Shi S, Yang G (September 2019). "Rev-erbα Inhibits Proliferation and Promotes Apoptosis of Preadipocytes through the Agonist GSK4112". International Journal of Molecular Sciences. 20 (18): 4524. doi:10.3390/ijms20184524. PMC 6769707. PMID 31547330.

[4] Kim K, Kim JH, Kim I, Seong S, Kim N (January 2020). "Rev-erbα Negatively Regulates Osteoclast and Osteoblast Differentiation through p38 MAPK Signaling Pathway". Molecules and Cells. 43 (1): 34–47. doi:10.14348/molcells.2019.0232. PMC 6999712. PMID 31896234.

[5] Sato S, Sakurai T, Ogasawara J, Takahashi M, Izawa T, Imaizumi K, et al. (January 2014). "A circadian clock gene, Rev-erbα, modulates the inflammatory function of macrophages through the negative regulation of Ccl2 expression". Journal of Immunology. 192 (1): 407–17. doi:10.4049/jimmunol.1301982. PMID 24307731.

[6] Sundar IK, Rashid K, Sellix MT, Rahman I (December 2017). "The nuclear receptor and clock gene REV-ERBα regulates cigarette smoke-induced lung inflammation". Biochemical and Biophysical Research Communications. 493 (4): 1390–1395. doi:10.1016/j.bbrc.2017.09.157. PMC 5756581. PMID 28974420.

[7] Guo DK, Zhu Y, Sun HY, Xu XY, Zhang S, Hao ZB, et al. (January 2019). "Pharmacological activation of REV-ERBα represses LPS-induced microglial activation through the NF-κB pathway". Acta Pharmacologica Sinica. 40 (1): 26–34. doi:10.1038/s41401-018-0064-0. PMC 6318300. PMID 29950615.

[8] Morioka N, Kodama K, Tomori M, Yoshikawa K, Saeki M, Nakamura Y, et al. (May 2019). "Stimulation of nuclear receptor REV-ERBs suppresses production of pronociceptive molecules in cultured spinal astrocytes and ameliorates mechanical hypersensitivity of inflammatory and neuropathic pain of mice" (PDF). Brain, Behavior, and Immunity. 78: 116–130. doi:10.1016/j.bbi.2019.01.014. PMID 30682503. S2CID 59273997.

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References