GW-1100

GW-1100
Identifiers
	IUPAC name ethyl 4-[5-[(2-ethoxypyrimidin-5-yl)methyl]-2-[(4-fluorophenyl)methylsulfanyl]-4-oxopyrimidin-1-yl]benzoate;
CAS Number	306974-70-9;
PubChem CID	11692123;
CompTox Dashboard (EPA)	DTXSID80470686 ;
Chemical and physical data
Formula	C27H25FN4O4S
Molar mass	520.58 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCOC1=NC=C(C=N1)CC2=CN(C(=NC2=O)SCC3=CC=C(C=C3)F)C4=CC=C(C=C4)C(=O)OCC;
	InChI InChI=1S/C27H25FN4O4S/c1-3-35-25(34)20-7-11-23(12-8-20)32-16-21(13-19-14-29-26(30-15-19)36-4-2)24(33)31-27(32)37-17-18-5-9-22(28)10-6-18/h5-12,14-16H,3-4,13,17H2,1-2H3; Key:PTPNCCWOTBBVJR-UHFFFAOYSA-N;

GW-1100 (GW1100) is an experimental drug which acts as a potent and selective antagonist for the free fatty acid receptor FFAR1 (GPR40). Agonists for this receptor have potentially useful antiinflammatory and anti-fibrotic effects, and while GW-1100 does not have therapeutic effects in its own right, it is important for research into the FFAR1 receptor as it allows comparison testing to measure the effectiveness of FFAR1 agonists.^[1]^[2]^[3]^[4]^[5]^[6]^[7] GW-1100 also showed inhibition of cancer cell growth in vitro, suggesting potential applications of FFAR1 antagonists in the treatment of cancer.^[8]^[9]

References

^ Briscoe CP, Peat AJ, McKeown SC, Corbett DF, Goetz AS, Littleton TR, McCoy DC, Kenakin TP, Andrews JL, Ammala C, Fornwald JA, Ignar DM, Jenkinson S. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br J Pharmacol. 2006 Jul;148(5):619-28. doi:10.1038/sj.bjp.0706770 PMID 16702987
^ Nakamoto K, Nishinaka T, Sato N, Mankura M, Koyama Y, Kasuya F, Tokuyama S. Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain. PLoS One. 2013 Dec 12;8(12):e81563. doi:10.1371/journal.pone.0081563 unflagged free DOI (link) PMID 24349089
^ Lin C, Chao H, Li Z, Xu X, Liu Y, Bao Z, Hou L, Liu Y, Wang X, You Y, Liu N, Ji J. Omega-3 fatty acids regulate NLRP3 inflammasome activation and prevent behavior deficits after traumatic brain injury. Exp Neurol. 2017 Apr;290:115-122. doi:10.1016/j.expneurol.2017.01.005 PMID 28077335
^ Nakamoto K, Aizawa F, Miyagi K, Yamashita T, Mankura M, Koyama Y, Kasuya F, Hirasawa A, Kurihara T, Miyata A, Tokuyama S. Dysfunctional GPR40/FFAR1 signaling exacerbates pain behavior in mice. PLoS One. 2017 Jul 19;12(7):e0180610. doi:10.1371/journal.pone.0180610 unflagged free DOI (link) PMID 28723961
^ Aizawa F, Nakamoto K, Tokuyama S. The involvement of free fatty acid-GPR40/FFAR1 signaling in chronic social defeat stress-induced pain prolongation in C57BL/6J male mice. Psychopharmacology (Berl). 2018 Aug;235(8):2335-2347. doi:10.1007/s00213-018-4930-8 PMID 29931581
^ Gong Y, Chen J, Jin Y, Wang C, Zheng M, He L. GW9508 ameliorates cognitive impairment via the cAMP-CREB and JNK pathways in APPswe/PS1dE9 mouse model of Alzheimer's disease. Neuropharmacology. 2020 Mar 1;164:107899. doi:10.1016/j.neuropharm.2019.107899 PMID 31809762
^ Freitas RDS, Muradás TC, Dagnino APA, Rost FL, Costa KM, Venturin GT, Greggio S, da Costa JC, Campos MM. Targeting FFA1 and FFA4 receptors in cancer-induced cachexia. Am J Physiol Endocrinol Metab. 2020 Nov 1;319(5):E877-E892. doi:10.1152/ajpendo.00509.2019 PMID 32893672
^ Fukushima K, Takahashi K, Kusaka M, Ishimoto K, Minami K, Otagaki S, Fukushima N, Honoki K, Tsujiuchi T. Induction of GPR40 positively regulates cell motile and growth activities in breast cancer MCF-7 cells. J Recept Signal Transduct Res. 2018 Aug;38(4):311-315. doi:10.1080/10799893.2018.1494742 PMID 30111226
^ Takahashi K, Fukushima K, Onishi Y, Minami K, Otagaki S, Ishimoto K, Fukushima N, Honoki K, Tsujiuchi T. Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. Exp Cell Res. 2018 Aug 1;369(1):54-60. doi:10.1016/j.yexcr.2018.05.005 PMID 29750897

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[1] Briscoe CP, Peat AJ, McKeown SC, Corbett DF, Goetz AS, Littleton TR, McCoy DC, Kenakin TP, Andrews JL, Ammala C, Fornwald JA, Ignar DM, Jenkinson S. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br J Pharmacol. 2006 Jul;148(5):619-28. doi:10.1038/sj.bjp.0706770 PMID 16702987

[2] Nakamoto K, Nishinaka T, Sato N, Mankura M, Koyama Y, Kasuya F, Tokuyama S. Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain. PLoS One. 2013 Dec 12;8(12):e81563. doi:10.1371/journal.pone.0081563 unflagged free DOI (link) PMID 24349089

[3] Lin C, Chao H, Li Z, Xu X, Liu Y, Bao Z, Hou L, Liu Y, Wang X, You Y, Liu N, Ji J. Omega-3 fatty acids regulate NLRP3 inflammasome activation and prevent behavior deficits after traumatic brain injury. Exp Neurol. 2017 Apr;290:115-122. doi:10.1016/j.expneurol.2017.01.005 PMID 28077335

[4] Nakamoto K, Aizawa F, Miyagi K, Yamashita T, Mankura M, Koyama Y, Kasuya F, Hirasawa A, Kurihara T, Miyata A, Tokuyama S. Dysfunctional GPR40/FFAR1 signaling exacerbates pain behavior in mice. PLoS One. 2017 Jul 19;12(7):e0180610. doi:10.1371/journal.pone.0180610 unflagged free DOI (link) PMID 28723961

[5] Aizawa F, Nakamoto K, Tokuyama S. The involvement of free fatty acid-GPR40/FFAR1 signaling in chronic social defeat stress-induced pain prolongation in C57BL/6J male mice. Psychopharmacology (Berl). 2018 Aug;235(8):2335-2347. doi:10.1007/s00213-018-4930-8 PMID 29931581

[6] Gong Y, Chen J, Jin Y, Wang C, Zheng M, He L. GW9508 ameliorates cognitive impairment via the cAMP-CREB and JNK pathways in APPswe/PS1dE9 mouse model of Alzheimer's disease. Neuropharmacology. 2020 Mar 1;164:107899. doi:10.1016/j.neuropharm.2019.107899 PMID 31809762

[7] Freitas RDS, Muradás TC, Dagnino APA, Rost FL, Costa KM, Venturin GT, Greggio S, da Costa JC, Campos MM. Targeting FFA1 and FFA4 receptors in cancer-induced cachexia. Am J Physiol Endocrinol Metab. 2020 Nov 1;319(5):E877-E892. doi:10.1152/ajpendo.00509.2019 PMID 32893672

[8] Fukushima K, Takahashi K, Kusaka M, Ishimoto K, Minami K, Otagaki S, Fukushima N, Honoki K, Tsujiuchi T. Induction of GPR40 positively regulates cell motile and growth activities in breast cancer MCF-7 cells. J Recept Signal Transduct Res. 2018 Aug;38(4):311-315. doi:10.1080/10799893.2018.1494742 PMID 30111226

[9] Takahashi K, Fukushima K, Onishi Y, Minami K, Otagaki S, Ishimoto K, Fukushima N, Honoki K, Tsujiuchi T. Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. Exp Cell Res. 2018 Aug 1;369(1):54-60. doi:10.1016/j.yexcr.2018.05.005 PMID 29750897

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