Description
TG101348 is an inhibitor of JAK2 that is currently in clinical trials as a potential treatment for myelofibrosis. TG101348 exhibits immunomodulatory and anticancer chemotherapeutic activities. In cells acquired from acute coronary syndrome patients, TG101348 decreases expression of Th17 cells and increases expression of Treg cells. TG101348 inhibits cellular proliferation of Hodgkin lymphoma cells and mediastinal large B-cell lymphoma cells; in vivo, this compound decreases tumor growth and increases survival. In animal models of myeloproliferative disease, TG101348 decreases hematocrit and leukocyte count, somewhat attenuating myelofibrosis.
References
Zheng Y, Wang Z, Deng L, et al. Modulation of STAT3 and STAT5 activity rectifies the imbalance of Th17 and Treg cells in patients with acute coronary syndrome. Clin Immunol. 2015 Jan 5;157(1):65-77. PMID: 25572535.
Hao Y, Chapuy B, Monti S, et al. Selective JAK2 inhibition specifically decreases Hodgkin lymphoma and mediastinal large B-cell lymphoma growth in vitro and in vivo. Clin Cancer Res. 2014 May 15;20(10):2674-83. PMID: 24610827.
Zhang M, Xu CR, Shamiyeh E, et al. A randomized, placebo-controlled study of the pharmacokinetics, pharmacodynamics, and tolerability of the oral JAK2 inhibitor fedratinib (SAR302503) in healthy volunteers. J Clin Pharmacol. 2014 Apr;54(4):415-21. PMID: 24165976.
Wernig G, Kharas MG, Okabe R, et al. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell. 2008 Apr;13(4):311-20. PMID: 18394554.
