Janus kinase inhibitor
Encyclopedia
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 (JAK1, JAK2, JAK3, TYK2), interfering with the JAK-STAT signaling pathway
.
Some JAK2 inhibitors are under development for the treatment of polycythemia vera
, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
.
Some inhibitors of JAK2 are in clinical trials, e.g. for psoriasis
.
JAK3 is also being targeted for a variety of inflammatory diseases, and one has had good results in a phase II trial for rheumatoid arthritis
.
Janus kinase
Janus kinase is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 & 2 , but were ultimately published as "Janus kinase"...
family of enzymes (JAK1, JAK2, JAK3, TYK2), interfering with the JAK-STAT signaling pathway
JAK-STAT signaling pathway
The JAK-STAT signaling pathway transmits information from chemical signals outside the cell, through the cell membrane, and into gene promoters on the DNA in the cell nucleus, which causes DNA transcription and activity in the cell. The JAK-STAT system is a major signaling alternative to the second...
.
Some JAK2 inhibitors are under development for the treatment of polycythemia vera
Polycythemia vera
Polycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...
, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
Myelofibrosis
Myelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...
.
Some inhibitors of JAK2 are in clinical trials, e.g. for psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...
.
JAK3 is also being targeted for a variety of inflammatory diseases, and one has had good results in a phase II trial for rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
.
Examples
- LestaurtinibLestaurtinibLestaurtinib is a tyrosine kinase inhibitor structurally related to staurosporine, and is being developed by Cephalon.It is an inhibitor of FLT3, JAK2, TrkA, TrkB and TrkC.-Uses:...
against JAK2, for acute myelogenous leukemia (AML) - TofacitinibTofacitinibTofacitinib is a drug being investigated by Pfizer for the treatment of rheumatoid arthritis , psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection...
(previously called tasocitinib) (CP-690550) against JAK3 for psoriasisPsoriasisPsoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...
, and rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
. Early Phase III results in November 2010 were encouraging. - Ruxolitinib against JAK1/JAK2 for psoriasis, myelofibrosisMyelofibrosisMyelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...
, and rheumatoid arthritis - Pacritinib (SB1518) against JAK2 for relapsed lymphomaLymphomaLymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
, advanced myeloidMyeloidThe term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
malignancies, myelofibrosisMyelofibrosisMyelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...
and CIMF Phase II results for polycythemia veraPolycythemia veraPolycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...
and thrombocythemia myelofibrosis - CYT387 against JAK2 for myeloproliferative disorders
- LY3009104 (INCB28050) against JAK1/JAK2 starting phase IIb for rheumatoid arthritis
- TG101348TG101348TG101348 is an orally available inhibitor of Janus kinase 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...
against JAK2; phase I results for myelofibrosisMyelofibrosisMyelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...
are published