Publications & Posters

RORyt

Publications

Identification and biological evaluation of thiazole-based inverse agonists of RORγt.

Gege C, Cummings MD, Albers M, Kinzel O, Kleymann G, Schlüter T, Steeneck C, Nelen MI, Milligan C, Spurlino J, Xue X, Leonard K, Edwards JP, Fourie A, Goldberg SD, Hoffmann T.
Bioorg Med Chem Lett. 2018 May 15;28(9):1446-1455. Epub 2018 Apr 3.

Pharmacologic modulation of RORγt translates to efficacy in preclinical and translational models of psoriasis and inflammatory arthritis.

Xue X, Soroosh P, De Leon-Tabaldo A, Luna-Roman R, Sablad M, Rozenkrants N, Yu J, Castro G, Banie H, Fung-Leung WP, Santamaria-Babi L, Schlüter T, Albers M, Leonard K, Budelsky AL, Fourie AM.
Sci Rep. 2016 Dec 1;6:37977.

Posters

Identification of the first inverse agonist of retinoid-related orphan receptor (ROR) with dual selectivity for RORβ and RORγt

Gege C, Schlüter T, Hoffmann T.
Bioorg Med Chem Lett. 2014 Nov 15;24(22):5265-7. Epub 2014 Sep 28.

FXR

Publications

Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice.

de Boer JF, Schonewille M, Boesjes M, Wolters H, Bloks VW, Bos T, van Dijk TH, Jurdzinski A, Boverhof R, Wolters JC, Kuivenhoven JA, van Deursen JM, Oude Elferink RPJ, Moschetta A, Kremoser C, Verkade HJ, Kuipers F, Groen AK.
Gastroenterology. 2017 Apr;152(5):1126-1138. Epub 2017 Jan 5.

The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.

Schwabl P, Hambruch E, Seeland BA, Hayden H, Wagner M, Garnys L, Strobel B, Schubert TL, Riedl F, Mitteregger D, Burnet M, Starlinger P, Oberhuber G, Deuschle U, Rohr-Udilova N, Podesser BK, Peck-Radosavljevic M, Reiberger T, Kremoser C, Trauner M.
J Hepatol. 2017 Apr;66(4):724-733. Epub 2016 Dec 18.

Novel substituted isoxazole FXR agonists with cyclopropyl, hydroxycyclobutyl and hydroxyazetidinyl linkers: Understanding and improving key determinants of pharmacological properties.

Kinzel O, Steeneck C, Schlüter T, Schulz A, Gege C, Hahn U, Hambruch E, Hornberger M, Spalwisz A, Frick K, Perovic-Ottstadt S, Deuschle U, Burnet M, Kremoser C.
Bioorg Med Chem Lett. 2016 Aug 1;26(15):3746-53. Epub 2016 May 24.

The nuclear bile acid receptor FXR controls the liver derived tumor suppressor histidine-rich glycoprotein.

Deuschle U, Birkel M, Hambruch E, Hornberger M, Kinzel O, Perovic-Ottstadt S, Schulz A, Hahn U, Burnet M, Kremoser C.
Int J Cancer. 2015 Jun 1;136(11):2693-704. Epub 2014 Nov 13.

Knocking on FXR’s door: the “hammerhead”-structure series of FXR agonists – amphiphilic isoxazoles with potent in vitro and in vivo activities.

Gege C, Kinzel O, Steeneck C, Schulz A, Kremoser C.
Curr Top Med Chem. 2014;14(19):2143-58. Review.

Posters

GS-9674 shows reduced side effect profile in mice, monkeys and human phase I studies compared to its predecessor Px-102

EASL The International Liver Congress 2019, April 10-14, Vienna, Austria

From mice to men – Plasma and fecal bile acid composition as sensitive markers of pharmacological FXR activation: Results from animal and human phase I studies using the potent and selective FXR agonist PX20606.

European Association for the Study of the Liver: “The International Liver Congress™ 2016”, April 13-17, 2016, Barcelona, Spain

FXR controls the tumor suppressor Histidine Rich Glycoprotein (HRG).

Falk Symposium 194: “XXIII International Bile. Acid Meeting: Bile Acids as Signal Integrators and. Metabolic Modulators”, October 89, 2014 Freiburg, Germany

FXR agonist Px-102 improves hepatic steatosis in NAFLD mouse models.

The Asian Pacific Association for the Study of the Liver: “APASL Liver week”, Juni 6-10, 2013 Singapore, Malysia

Synthetic Farnesoid X Receptor agonist PX20606 demonstrates anti-atherosclerotic effects and lowers cholesterol in HDL2 but not in HDL3 subfractions.

DKFZ-ZMBH Alliance Forum: “Metabolism 2012 From Signaling to Disease”, November 15-16, 2012 Heidelberg, Germany

Strong anti-steatotic and anti-fibrotic effects of novel FXR agonists in a murine NASH model that resembles human NASH.

The 9th JSH Single Topic Conference :”NASH 2010″ November 18-19, 2010 Tokyo, Japan

LXR

Publications

A Novel Principle for Partial Agonism of Liver X Receptor Ligands: COMPETITIVE RECRUITMENT OF ACTIVATORS AND REPRESSORS.

Albers M, Blume B, Schlueter T, Wright MB,
Kober I, Kremoser C, Deuschle U, Koegl M.
J Biol Chem. 2006 Feb 24;281(8):4920-30. Epub 2005 Dec 13.

Posters

Liver X Receptor (LXR) inverse agonist PX665 for NAFLD/NASH

Discovery on Target 2019, September 16-19, Boston, MA, USA

Unexpected anti-diabetic effects and anti-fibrotic activities of LXR inverse agonists in mouse models of NADFLD/NASH

American Association for the Study of the Liver Diseases: “The Liver Meeting™ 2018”, November 9-13, 2018 San Francisco, USA

LXR inverse agonists inhibit de novo lipogenesis and reduce intestinal lipid and cholesterol absorption in a NAFLD mouse model.

European Association for the Study of the Liver: “The International Liver Congress™ 2018”, April 11-15, 2018, Paris, France

LXR inverse agonists demonstrate liver lipid lowering effects through multiple mechanisms in rodent models of NASH and in human hepatocytes.

NASH tag conference 2017, January 5-7, Utah, USA

Novel LXR inverse agonists demonstrate anti-steatotic effects in human hepatocytes and in rodent models of NAFLD.

American Association for the Study of the Liver Diseases: “The Liver Meeting™ 2016”, November 11-15, 2016 Boston, USA

AHR / IDO

Publications

Discovery of Hydroxyamidine Based Inhibitors of IDO1 for Cancer Immunotherapy with Reduced Potential for Glucuronidation.

Steeneck C, Kinzel O, Anderhub S, Hornberger M, Pinto S, Morschhaeuser B, Braun F, Kleymann G, Hoffmann T.
ACS Med Chem Lett. 2020 Jan 27;11(2):179-187. eCollection 2020 Feb 13.