Publications

TGFß in GI Fibrosis

AGMB-129, an investigational ALK5 inhibitor for the treatment of Fibrostenosing Crohn’s Disease (FSCD),shows gastrointestinal(GI)restricted pharmacokinetics(PK) and a favorable safety profile in healthy subjects
Giovanni Latella, Florian Rieder. Intestinal fibrosis: Ready to be Reversed. Curr Opin Gastroenterol. 2017 July ; 33(4): 239–245.
G Latella, A Vetuschi, R Sferra, G Zanninelli, A D’Angelo, V Catitti, R Caprilli, K C Flanders, E Gaudio. Smad3 loss confers resistance to the development of trinitrobenzene sulfonic acid-induced colorectal fibrosis. Eur J Clin Invest. 2009 Feb;39(2):145-56.
Yun SM, Kim SH, Kim EH. The Molecular Mechanism of Transforming Growth Factor-β Signaling for Intestinal Fibrosis: A Mini-Review Review. Front Pharmacol. 2019 Feb 27;10:162. doi: 10.3389/fphar.2019.00162 PMID: 30873033
Vallance BA, Gunawan MI, Hewlett B, Bercik P, Van Kampen C, Galeazzi F, Sime PJ, Gauldie J, Collins SM. TGF-beta1 gene transfer to the mouse colon leads to intestinal fibrosis. Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G116-28. doi: 10.1152/ajpgi.00051.2005 PMID: 15778431
Di Sabatino A, Jackson CL, Pickard KM, Buckley M, Rovedatti L, Leakey NAB, Picariello L, Cazzola P, Monteleone G, Tonelli F, Corazza GR, MacDonald TT, Pender SL. Transforming growth factor beta signalling and matrix metalloproteinases in the mucosa overlying Crohn’s disease strictures Gut. 2009 Jun;58(6):777-89. doi: 10.1136/gut.2008.149096 PMID: 19201776
Rieder F, Fiocchi C, Rogler G. Mechanisms, Management, and Treatment of Fibrosis in Patients with Inflammatory Bowel Diseases. Gastroenterology. 2017 Feb;152(2):340-350.e6. doi: 10.1053/j.gastro.2016.09.047 PMID: 27720839

TGFß in IPF

Fernandez IE, Eickelberg O. The impact of TGF-beta on lung fibrosis: from targeting to biomarkers. Proc Am Thorac Soc. 2012 Jul;9(3):111-6. doi: 10.1513/pats.201203-023AW PMID: 22802283
Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J. Adenovector mediated gene transfer of active transforminggrowth factor β1 induces prolonged severe fibrosis in rat lung. J Clin Invest. 1997;100:768-776. doi: 10.1172/JCI119590 PMID: 9259574
Zhao J, Shi W, Wang YL, Chen H, Bringas P Jr, Datto MB, Frederick JP, Wang XF, Warburton. Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice. Am J Physiol Lung Cell Mol Physiol. 2002;282:L585–L593. doi: 10.1152/ajplung.00151.2001 PMID: 11839555
Li M, Krishnaveni MS, Li C, Zhou B, Xing Y, Banfalvi A, Li A, Lombardi V, Akbari O, Borok Z, Minoo P. Epithelium-specific deletion of TGF-b receptor type II protects mice from bleomycin induced pulmonary fibrosis. J Clin Invest. 2011;121:277–287. doi: 10.1172/JCI42090 PMID: 21135509
Higashiyama H, Yoshimoto D, Kaise T, Matsubara S, Fujiwara M, Kikkawa H, Asano S, Kinoshita M. Inhibition of activin receptor-like kinase 5 attenuates bleomycin-induced pulmonary fibrosis. Exp Mol Pathol. 2007 Aug;83(1):39-46. doi: 10.1016/j.yexmp.2006.12.003 PMID: 17274978

TGFß in Liver Fibrosis

Fabregat I, Moreno-Càceres J, Sánchez A, Dooley S, Dewidar B, Giannelli G, Ten Dijke P, IT-LIVER Consortium. TGF-beta signalling and liver disease. FEBS J. 2016 Jun;283(12):2219-32. doi: 10.1111/febs.13665 PMID: 26807763

Toxicity of systemic TGFß blockade

Anderton MJ, Mellor HR, Bell A, Sadler C, Pass M, Powell S, Steele SJ, Roberts RRA, Heier A. Induction of heart valve lesions by small-molecule ALK5 inhibitors. Toxicol Pathol. 2011 Oct;39(6):916-24. doi: 10.1177/0192623311416259 PMID: 21859884
Stauber AJ, Credille KM, Truex LL, Ehlhardt WJ, Young JK. Nonclinical Safety Evaluation of a Transforming Growth Factor β Receptor I Kinase Inhibitor in Fischer 344 Rats and Beagle Dogs. J Clin Pract 2014;4:3. doi: 10.4172/2161-0495.196

HGF/ MET Pathway Overview

Nakamura T, Sakai K, Nakamura T, Matsumoto K. Hepatocyte growth factor twenty years on: Much more than a growth factor. J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:188-202. doi: 10.1111/j.1440-1746.2010.06549.x. PMID: 21199531.
Matsumoto K, Funakoshi H, Takahashi H, Sakai K. HGF-Met Pathway in Regeneration and Drug Discovery. Biomedicines. 2014 Oct 31;2(4):275-300. doi: 10.3390/biomedicines2040275. PMID: 28548072; PMCID: PMC5344275.
Nakamura T, Mizuno S. The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(6):588-610. doi: 10.2183/pjab.86.588. PMID: 20551596; PMCID: PMC3081175.
Sakai K, Aoki S, Matsumoto K. Hepatocyte growth factor and Met in drug discovery. J Biochem. 2015 May;157(5):271-84. doi: 10.1093/jb/mvv027. Epub 2015 Mar 13. PMID: 25770121.

HGF/ MET Pathway in Disease

Ueki T, Kaneda Y, Tsutsui H, Nakanishi K, Sawa Y, Morishita R, Matsumoto K, Nakamura T, Takahashi H, Okamoto E, Fujimoto J. Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nat Med. 1999 Feb;5(2):226-30. doi: 10.1038/5593. PMID: 9930873.
Yamaji N, Ido A, Moriuchi A, Numata M, Setoyama H, Tamai T, Funakawa K, Fujita H, Sakiyama T, Uto H, Oketani M, Tsubouchi H. Hepatocyte growth factor ameliorates mucosal injuries leading to inhibition of colon cancer development in mice. Oncol Rep. 2011 Aug;26(2):335-41. doi: 10.3892/or.2011.1294. Epub 2011 May 4. PMID: 21567095.
Liu Y. Hepatocyte growth factor in kidney fibrosis: therapeutic potential and mechanisms of action. Am J Physiol Renal Physiol. 2004 Jul;287(1):F7-16. doi: 10.1152/ajprenal.00451.2003. PMID: 15180923.
de Andrade JA, Thannickal VJ. Innovative approaches to the therapy of fibrosis. Curr Opin Rheumatol. 2009 Nov;21(6):649-55. doi: 10.1097/BOR.0b013e328330da9b. PMID: 19667993; PMCID: PMC2862988.
Alvarez-Perez JC, Ernst S, Demirci C, Casinelli GP, Mellado-Gil JM, Rausell-Palamos F, Vasavada RC, Garcia-Ocaña A. Hepatocyte growth factor/c-Met signaling is required for β-cell regeneration. Diabetes. 2014 Jan;63(1):216-23. doi: 10.2337/db13-0333. Epub 2013 Oct 2. PMID: 24089510; PMCID: PMC3868042.

Disclaimer

The publications reflect historical data. Agomab does not warrant that these data are accurate, complete or up-to-date as of the date you access such publications. All Agomab product candidates mentioned in these publications are investigational in nature and have not been approved yet by any regulatory authority. Their efficacy and safety have not been established. The content of these publications is not intended for patients. Patients should always consult with a doctor or other healthcare professionals for medical advice or information about diagnosis and treatment.