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Emricasan Clinical Publications

Clinical trial: the efficacy and safety of oral PF-03491390, a pancaspase inhibitor – a randomized placebo-controlled study in patients with chronic hepatitis C
M.L. Shiffman, P. Pockros, J.G. McHutchinson, E.R. Schiff, M. Morris, G. Burgess
Alimentary Pharmacology & Therapeutics Volume 31, Issue 9, pages 969–978, May 2010

Oral IDN-6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C.
Pockros PJ, Schiff ER, Shiffman ML, McHutchison JG, Gish RG, Afdhal NH, Makhviladze M, Huyghe M, Hecht D, Oltersdorf T, Shapiro DA.
Hepatology Volume 46, Issue 2, pages 324–329, August 2007

Emricasan Preclinical Publications

A Caspase Inhibitor, IDN-6556, Ameliorates Early Hepatic Injury in an Ex Vivo Rat Model of Warm and Cold Ischemia
Niel C. Hoglen, Dean M. Anselmo, Masamichi Katori, Marian Kaldas, Xiu-Da Shen, Karen L. Valentino, Charles Lassman, Ronald W. Busuttil, Jerzy W. Kupiec-Weglinski, and Douglas G. Farmer
Liver Transplantation Volume 13, Issue 3, pages 361–366, March 2007

Characterization of IDN-6556 (3-{2-(2-tert-Butylphenylaminooxalyl)-amino]-propionylamino}-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid): a Liver-Targeted Caspase Inhibitor
Niel C. Hoglen, Long-Shiuh Chen, Craig D. Fisher, Brad P. Hirakawa, Todd Groessl, and Patricia C. Contreras
JPET May 2004 vol. 309 no. 2 634-640

Caspase Inhibition Improves Ischemia-Reperfusion Injury After Lung Transplantation
Syed M. Quadri, Lorne Segall, Marc de Perrot, Bing Hana, Vernon Edwards, Nicola Jones, Thomas K. Waddell, Mingyao Liu and Shaf Keshavjee,
American Journal of Transplantation Volume 5, Issue 2, pages 292–299, February 2005

Orally-Administered Caspase Inhibitor PF-03491390 Is Retained in the Liver for Prolonged Periods With Low Systemic Exposure, Exerting a Hepatoprotective Effect Against a-Fas-Induced Liver Injury in a Mouse Model
Yoshinobu Ueno, Takashi Ohmi, Mitsuko Yamamoto, Naoto Kato, Yukiko Moriguchi, Midori Kojima, Rieko Shimozono, Sachiko Suzuki, Tomomi Matsuura, and Hiroyuki Eda
J Pharmacol Sci. 2007 Oct;105(2):201-5. Epub 2007 Oct 6.

The Caspase Inhibitor IDN-6556 Attenuates Hepatic Injury and Fibrosis in the Bile Duct Ligated Mouse
Ali Canbay, Ariel Feldstein, Edwina Baskin-Bey, Steven F. Bronk, and Gregory J. Gores
Journal of Pharmacology and Experimental Therapeutics . 04/2004; 308(3):1191-6.

Posters & Abstracts

Physiologically normal levels of apoptosis in healthy volunteers are not reduced by the pan-caspase inhibitor, emricasan
Alfred P. Spada*, Patricia C. Contreras, MiRa C. Huyghe, Mark Morris and Gary C. Burgess
AASLD Poster November 2013

PF-03491390 Pan-Caspase Inhibitor Decreases Liver Injury and Fibrosis in a Murine Model of Non-Alcoholic Steatohepatitis (NASH)
Barreyro, Fernando J; Holod, Silvia; Finocchietto, Paola V; Camino, Alejandra M; Aquino, Jorge B; Avagnina, Alejandra; Carreras, María Cecilia; Poderoso, Juan José; Gores, Gregory J
Poster Presented at EASL April 2010

Pan-Caspase Inhibition Protects Against Fibrotic NASH Induced By Choline Deficient Amino Acid Defined Diet (CDAA)
W. Lu, A. Eguchi, D. Sirbu, P. Contreras, C. Johnson, A. Wree, D. Povero, M. Lazic, and A. Feldstein
Poster Presented at EASL April 2013

Safety and Efficacy of the Pan-Caspase Inhibitor IDN-6556 on the Treatment of Non-Alcoholic Fatty Liver and Insulin Resistance
W. Lu, A. Eguchi, D. Sirbu, P. Contreras, C. Johnson, A. Wree, D. Povero, M. Lazic, and A. Feldstein
Poster Presented at EASL April 2013

Ishak Stage and Quantitative Fibrosis Measurement (Collagen Proportionate Area) Progression in Post Liver Transplant (post-LT) Patients with Chronic Hepatitis C Infection.
Guangli Ma, Andrew R. Hall, Anna C. Green, Pinelopi Manousou, Emmanuel Tsochatzis, Jeremy Gale, Gary Burgess, Andrew K Burroughs, Amar P. Dhillon
Poster Presented at World Congress of Pharmacology 2012

Inhibition of Caspase Activity with Emricasan in HCV Patients: Potential Implications for Chronic Dosing and Long Term Safety
Alfred P. Spada, Patricia Contreras, Gary C. Burgess
Poster Presented at ASLD November 2012

PF-03491390 Inhibits Liver Fibrosis in Patients With Chronic Hepatitis C Virus Infection Via Suppression of Pro-Apoptotic Caspase-Activation.
Gary Burgess, Peter Colman, Emanuel Engmann, Heike Bantel, Paresh N. Soni
AASLD Abstract 1307, October 2007

Apoptosis Resources

Kupffer Cell Engulfment of Apoptotic Bodies Stimulates Death Ligand and Cytokine Expression
Ali Canbay, Ariel E. Feldstein, Hajime Higuchi, Nate Werneburg, Annette Grambihler, Steve F. Bronk, and Gregory J. Gores
Hepatology Volume 38, Issue 5, pages 1188–1198, November 2003

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
L Galluzzi, I Vitale, JM Abrams, ES Alnemri, EH Baehrecke, MV Blagosklonny, TM Dawso, VL Dawson, WS El-Deiry, S Fulda, E Gottlieb, DR Green, MO Hengartner, O Kepp, RA Knight, S Kumar, SA Lipton, X Lu, F Madeo, W Malorni, P Mehlen, G Nunez, ME Peter, M Piacentini, DC Rubinsztein, Y Shi, H-U Simon, P Vandenabeele, E White, J Yuan, B Zhivotovsky, G Melino and G Kroemer
Cell Death and Differentiation (2012) 19, 107–120

Apoptosis and acute kidney injury
Andrea Havasi1 and Steven C. Borkan
Kidney International (2011) 80, 29–40; published online 11 May 2011

Genome-Wide Association Study Identifies Variants Associated With Progression of Liver Fibrosis From HCV Infection
Etienne Patin, Zoltán Kutalik, Julien Guergnon, Stéphanie Bibert, Bertrand Nalpas, Emmanuelle Jouanguy, Mona Munteanu, Laurence Bousquet, Laurent Argiro, Philippe Halfon, Anne Boland, Beat Müllhaupt, David Semela, Jean–François Dufour, Markus H. Heim, Darius Moradpour, Andreas Cerny, Raffaele Malinverni, Hans Hirsch, Gladys Martinetti, Vijayaprakash Suppiah, Graeme Stewart, David R. Booth, Jacob George, Jean–Laurent Casanova, Christian Bréchot, Charles M. Rice, Andrew H. Talal, Ira M. Jacobson, Marc Bourlière, Ioannis Theodorou, Thierry Poynard, Francesco Negro, Stanislas Pol, Pierre–Yves Bochud, Laurent Abe
Gastroenterology Volume 143, Issue 5 , Pages 1244-1252.e12, November 2012

Biomarker Resources

Reduction in Hepatic Inflammation Is Associated With Less Fibrosis Progression and Fewer Clinical Outcomes in Advanced Hepatitis C
Chihiro Morishima , MD, Mitchell L. Shiffman , MD, Jules L. Dienstag , MD, Karen L. Lindsay , MD, MMM, Gyongyi Szabo , MD, PhD,
Gregory T. Everson , MD 7 , Anna S. Lok , MD 8 , Adrian M. Di Bisceglie , MD 9 , Marc G. Ghany , MD, MHSc 10 , Deepa Naishadham , MA, MS 11 ,
Timothy R. Morgan , MD and Elizabeth C. Wright , PhD , for the HALT-C Trial Group
American Journal of Gastroenterology 2012; 107:1388–1398

Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study
Hyeon Chang Kim, Chung Mo Nam, Sun Ha Jee, Kwang Hyub Han, Dae Kyu Oh, Il Suh
British Medical Journal 2004;328:98

Serum Aminotransferase Activity and Mortality Risk in a United States Community
Tae Hoon Lee, W. Ray Kim, Joanne T. Benson, Terry M. Therneau, and L. Joseph Melton III
Hepatology Volume 47, Issue 3, pages 880–887, March 2008

Elevated serum CK18 levels in chronic hepatitis C patients are associated with advanced fibrosis but not steatosis
A. B. Jazwinski, A. J. Thompson, P. J. Clark, S. Naggie, H. L. Tillmann and K. Patel
Journal of Viral Hepatitis Volume 19, Issue 4, pages 278–282, April 2012

Serum Activity of Alanine Aminotransferase (ALT) as an Indicator of Health and Disease
W. Ray Kim, Steven L. Flamm, Adrian M. Di Bisceglie, and Henry C. Bodenheimer, Jr.
Hepatology Volume 47, Issue 4, pages 1363–1370, April 2008

Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C
W. B. Kronenberger, M. von Wagner, E. Herrmann, U. Mihm, A. Piiper, C. Sarrazin1 and S. Zeuzem
Journal of Viral Hepatitis Volume 12, Issue 3, pages 307–314, May 2005

ACLF Resources

Monitoring oxidative stress in acute-on-chronic liver failure by advanced oxidation protein productshepr_911 171..180
Hua Liu, Tao Han, Jie Tian, Zheng-Yan Zhu, Ying Liu, Yan Li, Shi-Xiang Xiao, Ying Li and Yu-Ying Feng
Hepatology Research Volume 42, Issue 2, pages 171–180, February 2012

Acute-on-Chronic Liver Failure Is a Distinct Syndrome That Develops in Patients With Acute Decompensation of Cirrhosis
Richard Moreau, Rajiv Jalan, Pere Gines, Marco Pavesi, Paolo Angeli, Juan Cordoba, Francois Durand, Thierry Gustot, Faouzi Saliba, Marco Domenicali, Alexander Gerbes, Julia Wendon, Carlo Alessandria, Wim Laleman, Stefan Zeuzem, Jonel Trebicka, Mauro Bernardi, Vicente Arroyo
Gastroenterology Volume 144, Issue 7 , Pages 1426-1437.e9, June 2013

Liver histology as predictor of outcome in patients with acute-on-chronic liver failure (ACLF)
Archana Rastogi, Ashish Kumar, Puja Sakhuja, Chhagan Bihari, Ranjana Gondal, Syed Hissar, Hitendra Garg, Shiv Kumar Sarin
Virchows Archiv August 2011, Volume 459, Issue 2, pp 121-127

CLF Resources

Elevated apoptosis-associated cytokeratin 18 fragments (CK18Asp386) in serum of patients with chronic liver diseases indicate hepatic and biliary inflammation
E. Yagmur, C. Trautwein, M.P.G. Leers, A.M. Gressner, F. Tacke
Clinical Biochemistry Volume 40, Issues 9–10, June 2007, Pages 651–655

HCV-POLT Resources

Progression of liver fibrosis in post-transplant hepatitis C: Mechanisms, assessment and treatment
Marina Berenguer, Detlef Schuppan
Journal of Hepatology Volume 58, Issue 5 , Pages 1028-1041, May 2013

Enhanced apoptosis in post-liver transplant hepatitis C: Effects of virus and immunosuppressants
Eu Jin Lim, Ruth Chin, Peter W Angus, and Joseph Torresi
World J Gastroenterol. 2012 May 14; 18(18): 2172–2179.

Accelerated liver disease in aggressive hepatitis C recurrence post-liver transplantation may be due to enhanced apoptosis mediated by both virus and immunosuppressants
Eu Jin Lim, Ruth Chin, Peter W. Angus, Joseph Torresi
Poster Presented at EASL April 2013