β-LGND2

Β-LGND2
Clinical data
Other names	β-LGND2; ER-β-selective ligand 2
Drug class	Nonsteroidal estrogen; Selective ERβ agonist
Identifiers
	IUPAC name 4-bromo-6,8-dihydroxy-2-(4-hydroxyphenyl)isoquinolin-1-one;
CAS Number	1462971-30-7 ; 1644567-26-9;
PubChem CID	24962206;
Chemical and physical data
Formula	C15H10BrNO4
Molar mass	348.152 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CC(=CC=C1N2C=C(C3=CC(=CC(=C3C2=O)O)O)Br)O;
	InChI InChI=1S/C15H10BrNO4/c16-12-7-17(8-1-3-9(18)4-2-8)15(21)14-11(12)5-10(19)6-13(14)20/h1-7,18-20H; Key:GLVQMSCCFOGRRG-UHFFFAOYSA-N;

β-LGND2, also known as ERβ-selective ligand 2 or as GTx-878, is a synthetic nonsteroidal estrogen and selective ERβ agonist which was under development by GTx for the treatment of benign prostatic hyperplasia, prostatitis, and rheumatoid arthritis but was never marketed.[1][2][3][4][5][6] It shows approximately 25-fold selectivity for activation of the ERβ over the ERα (EC₅₀ = 2 nM and 52 nM, respectively).[3] β-LGND2 is an isoquinolinone derivative.[2][5]

References

https://adisinsight.springer.com/drugs/800027855
Yepuru M, Eswaraka J, Kearbey JD, Barrett CM, Raghow S, Veverka KA, Miller DD, Dalton JT, Narayanan R (October 2010). "Estrogen receptor-{beta}-selective ligands alleviate high-fat diet- and ovariectomy-induced obesity in mice". J. Biol. Chem. 285 (41): 31292–303. doi:10.1074/jbc.M110.147850. PMC 2951204. PMID 20657011.
Ponnusamy S, Tran QT, Harvey I, Smallwood HS, Thiyagarajan T, Banerjee S, Johnson DL, Dalton JT, Sullivan RD, Miller DD, Bridges D, Narayanan R (January 2017). "Pharmacologic activation of estrogen receptor β increases mitochondrial function, energy expenditure, and brown adipose tissue". FASEB J. 31 (1): 266–281. doi:10.1096/fj.201600787RR. PMC 5161516. PMID 27733447. We found that β-LGND2, also known as GTx-878 (GTx, Inc. (31)), reduces body weight and fat mass without altering feed consumption of high-fat diet (HFD)-fed WT, but not ER-βKO, mice.
Giddabasappa A, Eswaraka JR, Barrett CM, Bauler MN, Wu Z, Yepuru M, Miller DD, Dalton JT (July 2012). "β-LGND2, an ERβ selective agonist, inhibits pathologic retinal neovascularization". Invest. Ophthalmol. Vis. Sci. 53 (8): 5066–75. doi:10.1167/iovs.12-9627. PMID 22714897.
Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F (November 2014). "Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential". Steroids. 90: 13–29. doi:10.1016/j.steroids.2014.06.012. PMC 4192010. PMID 24971815.
Mohler ML, Narayanan R, Coss CC, Hu K, He Y, Wu Z, Hong SS, Hwang DJ, Miller DD, Dalton JT (April 2010). "Estrogen receptor beta selective nonsteroidal estrogens: seeking clinical indications". Expert Opin Ther Pat. 20 (4): 507–34. doi:10.1517/13543771003657164. PMID 20302450.

External links

GTx-878 - AdisInsight

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[AdisInsight-1] ttps://adisinsight.springer.com/drugs/800027855

[pmid20657011-2] Yepuru M, Eswaraka J, Kearbey JD, Barrett CM, Raghow S, Veverka KA, Miller DD, Dalton JT, Narayanan R (October 2010). "Estrogen receptor-{beta}-selective ligands alleviate high-fat diet- and ovariectomy-induced obesity in mice". J. Biol. Chem. 285 (41): 31292–303. doi:10.1074/jbc.M110.147850. PMC 2951204. PMID 20657011.

[pmid27733447-3] Ponnusamy S, Tran QT, Harvey I, Smallwood HS, Thiyagarajan T, Banerjee S, Johnson DL, Dalton JT, Sullivan RD, Miller DD, Bridges D, Narayanan R (January 2017). "Pharmacologic activation of estrogen receptor β increases mitochondrial function, energy expenditure, and brown adipose tissue". FASEB J. 31 (1): 266–281. doi:10.1096/fj.201600787RR. PMC 5161516. PMID 27733447. We found that β-LGND2, also known as GTx-878 (GTx, Inc. (31)), reduces body weight and fat mass without altering feed consumption of high-fat diet (HFD)-fed WT, but not ER-βKO, mice.

[pmid22714897-4] Giddabasappa A, Eswaraka JR, Barrett CM, Bauler MN, Wu Z, Yepuru M, Miller DD, Dalton JT (July 2012). "β-LGND2, an ERβ selective agonist, inhibits pathologic retinal neovascularization". Invest. Ophthalmol. Vis. Sci. 53 (8): 5066–75. doi:10.1167/iovs.12-9627. PMID 22714897.

[pmid24971815-5] Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F (November 2014). "Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential". Steroids. 90: 13–29. doi:10.1016/j.steroids.2014.06.012. PMC 4192010. PMID 24971815.

[pmid20302450-6] Mohler ML, Narayanan R, Coss CC, Hu K, He Y, Wu Z, Hong SS, Hwang DJ, Miller DD, Dalton JT (April 2010). "Estrogen receptor beta selective nonsteroidal estrogens: seeking clinical indications". Expert Opin Ther Pat. 20 (4): 507–34. doi:10.1517/13543771003657164. PMID 20302450.