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;
CompTox Dashboard (EPA)	DTXSID401336369 ;
Chemical and physical data
Formula	C15H10BrNO4
Molar mass	348.152 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 (EC₅₀Tooltip half-maximal effective concentration = 2 nM and 52 nM, respectively).^[3] β-LGND2 is an isoquinolinone derivative.^[2]^[5]

References

^ "Research programme: Estrogen receptor beta agonists - Oncternal Therapeutics - AdisInsight".
^ ^a ^b 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.
^ ^a ^b 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.
^ ^a ^b 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. S2CID 314347.

External links

GTx-878 - AdisInsight

[AdisInsight-1] "Research programme: Estrogen receptor beta agonists - Oncternal Therapeutics - AdisInsight".

[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. S2CID 314347.

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