Β-LGND2

Chemical compound
Β-LGND2
Clinical data
Other namesβ-LGND2; ER-β-selective ligand 2
Drug classNonsteroidal estrogen; Selective ERβ agonist
Identifiers
  • 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 Edit this at Wikidata
Chemical and physical data
FormulaC15H10BrNO4
Molar mass348.152 g·mol−1
3D model (JSmol)
  • Interactive image
  • 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

  1. ^ "Research programme: Estrogen receptor beta agonists - Oncternal Therapeutics - AdisInsight".
  2. ^ 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.
  3. ^ 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.
  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.
  5. ^ 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.
  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.

External links

  • GTx-878 - AdisInsight


  • v
  • t
  • e
ERTooltip Estrogen receptor
Agonists
Mixed
(SERMsTooltip Selective estrogen receptor modulators)
Antagonists
  • Coregulator-binding modulators: ERX-11
GPERTooltip G protein-coupled estrogen receptor
Agonists
Antagonists
Unknown
See also
Receptor/signaling modulators
Estrogens and antiestrogens
Androgen receptor modulators
Progesterone receptor modulators
List of estrogens