Ruxolitinib

Potent and selective JAK1&2 inhibitor, IC50s=2.7, 4.5 and 322 nM forJAK1, JAK2 and JAK3 respectively [1]. Blocks IL-6 signaling (IC50=281 nM) and proliferation of JAK2V617F+ Ba/F3 cells (IC50=127 nM) [2]. Inhibits the proinflammatory secretome of senescent cells [3].The JAK1 S646P mutant is highly sensitive to ruxolitinib [4]. Clinically useful cancer chemotherapeutic.

References:

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