Biochemicals & reagents
1) Verstovsek et al. (2009), Therapeutic potential of JAK2 inhibitors; Hematology Am. Soc. Hematol. Educ. Program, 2009(1) 636 2) Quintas-Cardama et al. (2010), Preclinical characterization of the selective JAK1/2 inhibitor INCB01824: Therapeutic implications for the treatment of myeloproliferative neoplasms; Blood, 115 3109 3) Farr et al. (2017) Targeting cellular senescence prevents age-related bone loss in mice; Nat. Med., 23 1072 4) Li et al. (2017) Identification of a novel functional JAK1 S646P mutation in acute lymphoblastic leukemia; Oncotarget, 8 34687
Ruxolitinib is a potent and selective JAK1&2 inhibitor with IC50s=2.7, 4.5 and 322 nM for JAK1, JAK2 and JAK3 respectively (1). This compound blocks IL-6 signaling (IC50=281 nM) and proliferation of JAK2V617F+ Ba/F3 cells (IC50=127 nM) (2) and inhibits the proinflammatory secretome of senescent cells (3). The JAK1 S646P mutant is highly sensitive to ruxolitinib (4). It is a clinically relevant cancer chemotherapeutic.