TG101348
Encyclopedia
TG101348 is an orally available inhibitor of Janus kinase
2 (JAK-2) developed for the treatment of patients with myeloproliferative diseases including myelofibrosis
. TG101348 acts as a competitive inhibitor of protein kinase
JAK-2 with IC50=6 nM; related kinases FLT3 and RET are also sensitive, with IC50=25 nM and IC50=17 nM, respectively. Significantly less activity was observed against other tyrosine kinases including JAK3 (IC50=169 nM). In treated cells the inhibitor blocks downstream cellular signalling (JAK-STAT) leading to supression of proliferation and induction of apoptosis.
Myelofibrosis is a myeloid malignancy associated with anemia, splenomegaly, and constitutional symptoms. Patients with myelofibrosis frequently harbor JAK-STAT activating mutations that are sensitive to TG101348. Phase I trial results focused on safety and efficacy of TG101348 in patients with high- or intermediate-risk primary or post–polycythemia vera/essential thrombocythemia myelofibrosis have been published in 2011.
Compound was originally discovered TargeGen then acquired by Sanofi-Aventis
who continues its development under the code SAR302503.
Janus kinase inhibitor
Janus kinase inhibitor is a class of medicines that function by inhibiting the effect of one or more of the Janus kinase family of enzymes , interfering with the JAK-STAT signaling pathway....
2 (JAK-2) developed for the treatment of patients with myeloproliferative diseases including myelofibrosis
Myelofibrosis
Myelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...
. TG101348 acts as a competitive inhibitor of protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...
JAK-2 with IC50=6 nM; related kinases FLT3 and RET are also sensitive, with IC50=25 nM and IC50=17 nM, respectively. Significantly less activity was observed against other tyrosine kinases including JAK3 (IC50=169 nM). In treated cells the inhibitor blocks downstream cellular signalling (JAK-STAT) leading to supression of proliferation and induction of apoptosis.
Myelofibrosis is a myeloid malignancy associated with anemia, splenomegaly, and constitutional symptoms. Patients with myelofibrosis frequently harbor JAK-STAT activating mutations that are sensitive to TG101348. Phase I trial results focused on safety and efficacy of TG101348 in patients with high- or intermediate-risk primary or post–polycythemia vera/essential thrombocythemia myelofibrosis have been published in 2011.
Compound was originally discovered TargeGen then acquired by Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
who continues its development under the code SAR302503.