Background:

TG101209, a small-molecule identified by structure based design, is a selective inhibitor of janus kinase 2 (Jak2) that potently inhibits Jak/Stat pathway in multiple myeloma (MM) cell lines, such as cell harboring JAK2V617F or MPLW515L/K mutations which are commonly associated with polycythemia vera (PV) and primary myelofibrosis (PMF) respectively. According to results of multiple studies, it has revealed that TG101209 exhibits a dose and time dependent cyctoxicity, which is associated with inhibited cell cycle progrgression and induced apoptosis, in a wild range of MM cell lines through suppressing the expression of pJak2, pStat3 and Bcl-xl and inducing the overexpression of pErk and pAkt.

Reference

[1].Ramakrishnan V, Kimlinger T, Haug J, Timm M, Wellik L, Halling T, Pardanani A, Tefferi A, Rajkumar SV, Kumar S. TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells. Am J Hematol. 2010;85(9):675-686.