Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models

Reproductive Sciences
Stephen S PalmerSelvaraj G Nataraja

Abstract

Endometriosis is an estrogen (ER)-dependent gynecological disease caused by the growth of endometrial tissue at extrauterine sites. Current endocrine therapies address the estrogenic aspect of disease and offer some relief from pain but are associated with significant side effects. Immune dysfunction is also widely believed to be an underlying contributor to the pathogenesis of this disease. This study evaluated an inhibitor of c-Jun N-terminal kinase, bentamapimod (AS602801), which interrupts immune pathways, in 2 rodent endometriosis models. Treatment of nude mice bearing xenografts biopsied from women with endometriosis (BWE) with 30 mg/kg AS602801 caused 29% regression of lesion. Medroxyprogesterone acetate (MPA) or progesterone (PR) alone did not cause regression of BWE lesions, but combining 10 mg/kg AS602801 with MPA caused 38% lesion regression. In human endometrial organ cultures (from healthy women), treatment with AS602801 or MPA reduced matrix metalloproteinase-3 (MMP-3) release into culture medium. In organ cultures established with BWE, PR or MPA failed to inhibit MMP-3 secretion, whereas AS602801 alone or MPA + AS602801 suppressed MMP-3 production. In an autologous rat endometriosis model, AS602801 caused 48% reg...Continue Reading

References

Jan 1, 1992·Gynecologic and Obstetric Investigation·E TanakaM Hiroi
Dec 1, 1995·American Journal of Reproductive Immunology : AJRI·J A KeenanM R Caudle
Jul 7, 1999·Journal of Reproductive Immunology·L M Senturk, A Arici
Jul 8, 1999·Gynecologic and Obstetric Investigation·N UmesakiS Ogita
Feb 13, 2001·Fertility and Sterility·D I LebovicR N Taylor
Jul 5, 2001·Fertility and Sterility·T HaradaN Terakawa
Dec 4, 2003·Reproductive Biology and Endocrinology : RB&E·Cleophas M KyamaThomas M D'Hooghe
Mar 17, 2004·Fertility and Sterility·Breton F BarrierAnthony M Propst
Jul 17, 2004·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·A GallinelliA Volpe
Oct 27, 2004·Molecular Human Reproduction·K ShazandP Hugo
Nov 20, 2004·American Journal of Reproductive Immunology : AJRI·Osamu YoshinoYuji Taketani
Jan 18, 2005·Fertility and Sterility·Jason A EfstathiouMaria A Rupnick
Jan 13, 2006·Molecular and Cellular Endocrinology·Serdar E BulunJ Julie Kim
Nov 23, 2006·Reproductive Biology and Endocrinology : RB&E·Julie M Hastings, Asgerally T Fazleabas
Jun 14, 2008·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Laurent Peyrin-BirouletJean-Frédéric Colombel
Jan 16, 2009·The New England Journal of Medicine·Serdar E Bulun
Jan 28, 2010·Seminars in Reproductive Medicine·Serdar E BulunJ Julie Kim
Jan 29, 2010·Seminars in Reproductive Medicine·Serdar E BulunEmily J Su
May 4, 2010·The Journal of Pharmacology and Experimental Therapeutics·Z Melis AltanSelvaraj G Nataraja
Aug 20, 2010·Current Medical Research and Opinion·Kim Papp
Sep 22, 2010·Multiple Sclerosis : Clinical and Laboratory Research·Chiara FerrandiPaola F Zaratin
Nov 19, 2010·BJOG : an International Journal of Obstetrics and Gynaecology·Jennifer Mier-CabreraCésar Hernández-Guerrero
Dec 21, 2010·Histochemistry and Cell Biology·Yesim Hulya UzUmit Ali Kayisli
Sep 8, 2011·Expert Review of Clinical Immunology·Jennifer L HeringtonKevin G Osteen
Nov 17, 2011·Molecular and Cellular Endocrinology·Marwa Al-SabbaghJan J Brosens
Jan 30, 2013·Expert Opinion on Pharmacotherapy·Isabelle StreuliCharles Chapron
May 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Miles A MillerDouglas A Lauffenburger
Nov 1, 2013·Molecular Medicine Reports·Hiroshi KobayashiHirotaka Kajihara
Jan 18, 2014·Human Reproduction·G A J DunselmanUNKNOWN European Society of Human Reproduction and Embryology
Feb 7, 2014·Science Translational Medicine·Michael T BesteLinda G Griffith

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Citations

May 12, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Alexis D GreeneKatherine A Burns
Jul 6, 2018·Expert Opinion on Pharmacotherapy·Simone FerreroFabio Barra
Sep 19, 2020·American Journal of Reproductive Immunology : AJRI·Amelia P BaileyStacey A Missmer
Oct 24, 2018·Frontiers in Immunology·Nan Song, Tao Li
May 1, 2018·Expert Opinion on Investigational Drugs·Fabio BarraSimone Ferrero
Nov 12, 2020·Seminars in Reproductive Medicine·Juan S GneccoLinda G Griffith
Jan 23, 2021·Journal of Medicinal Chemistry·Zhouling XieChenzhong Liao
Feb 17, 2021·The Journal of Obstetrics and Gynaecology Research·Gizem Bora, Aylin Yaba
Dec 24, 2020·International Journal of Molecular Sciences·Stephanie Cristine Hepp RehfeldtStefan Laufer
May 20, 2021·Minerva Obstetrics and Gynecology·Simona MartoneStefano Luisi
Aug 28, 2021·International Journal of Molecular Sciences·Elisa GiacominiPaola Viganò

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Methods Mentioned

BETA
contraception
xenograft
biopsies
biopsy
Protein
electrophoresis
PCR
light microscopy
flow cytometry
Assay

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