PF-04965842 is an orally administered selective Janus kinase 1 (JAK1) inhibitor. PF-04965842 is currently in clinical trials for the treatment of autoimmune diseases.

Filgotinib (GLPG0634) is a highly selective JAK1 inhibitor. GLPG0634 is a promising drug candidate for the future treatment of autoimmune and inflammatory disorders. It is in phase III clinical trials (initiated mid-2016) for the treatment of rheumatoid arthritis, Crohn's disease and ulcerative colitis. Most common adverse events observed were infections, gastrointestinal disorders and nervous system disorders.

NS-018 is a potent inhibitor of Janus kinase 2 (JAK2) enzyme activity and Src-family kinases. It was developed as an oral therapy for the treatment of myelofibrosis. Overall NS-018 has been used in trials studying the treatment of primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia. NS-018 is a highly active JAK2 inhibitor, with an IC50 of 0.72 nM, 46-, 54-, and 31-fold selectivity for JAK2 over JAK1 (IC50, 33 nM), JAK3 (IC50, 39 nM), and Tyk2 (IC50, 22 nM). NS-018 also inhibits Src-family kinases, especially SRC and FYN, and weakly inhibits ABL and FLT3 with 45- and 90-fold selectivity for JAK2, respectively. NS-018 shows potent inhibitory activity against cell lines JAK2V617F or MPLW515L mutations or the TEL-JAK2 fusion gene.

PF-06700841 is an inhibitor of JAK1 and TYK2 kinases. PF-06700841 tosylate salt is potentially a treatment of systemic lupus erythematosus and plaque psoriasis.

Cerdulatinib is an oral, dual spleen tyrosine kinase (Syk) and janus kinase (JAK) inhibitor that uniquely inhibits two key cell signaling pathways that promote cancer cell growth in certain hematologic malignancies – the B-cell receptor pathway via Syk and key cytokine receptors via JAK Being developed to treat patients with hematologic cancers, specifically those who have relapsed or who have not responded to prior therapies. Cerdulatinib is in Phase 2 study evaluating the safety and efficacy of cerdulatinib in patients with relapsed/refractory B-cell malignancies who have failed multiple therapies.

Peficitinib (formerly known as ASP015K) is a pyrrolo[2,3-b]pyridine derivative orally administered once-daily JAK inhibitor in development for the treatment of Rheumatoid Arthritis. In preclinical studied Peficitinib inhibited JAK1 and JAK3 with IC50 of 3.9 and 0.7 nM, respectively. Peficitinib also inhibited IL-2-dependent T cell proliferation in vitro and STAT5 phosphorylation in vitro and ex vivo. Furthermore, Peficitinib dose-dependently suppressed bone destruction and paw swelling in an adjuvant-induced arthritis model in rats via prophylactic or therapeutic oral dosing regimens.In clinical trials, Peficitinib treatment prescribed at 50, 100 and 150 mg amounts each showed statistically significantly higher ACR20 response rates compared to the placebo and response rates increased up to the 150 mg dosage. Adverse events included neutropenia, headache, and abdominal pain. The treatment-emergent adverse events occurring more frequently in the Peficitinib group compared with the placebo group included diarrhea, nasopharyngitis, and increased serum creatine phosphokinase activity. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in the peficitinib 25 and 100 mg cohorts). The authors concluded that treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed an acceptable safety profile.

Cerdulatinib is an oral, dual spleen tyrosine kinase (Syk) and janus kinase (JAK) inhibitor that uniquely inhibits two key cell signaling pathways that promote cancer cell growth in certain hematologic malignancies – the B-cell receptor pathway via Syk and key cytokine receptors via JAK Being developed to treat patients with hematologic cancers, specifically those who have relapsed or who have not responded to prior therapies. Cerdulatinib is in Phase 2 study evaluating the safety and efficacy of cerdulatinib in patients with relapsed/refractory B-cell malignancies who have failed multiple therapies.

PF-06700841 is an inhibitor of JAK1 and TYK2 kinases. PF-06700841 tosylate salt is potentially a treatment of systemic lupus erythematosus and plaque psoriasis.

Filgotinib (GLPG0634) is a highly selective JAK1 inhibitor. GLPG0634 is a promising drug candidate for the future treatment of autoimmune and inflammatory disorders. It is in phase III clinical trials (initiated mid-2016) for the treatment of rheumatoid arthritis, Crohn's disease and ulcerative colitis. Most common adverse events observed were infections, gastrointestinal disorders and nervous system disorders.

NS-018 is a potent inhibitor of Janus kinase 2 (JAK2) enzyme activity and Src-family kinases. It was developed as an oral therapy for the treatment of myelofibrosis. Overall NS-018 has been used in trials studying the treatment of primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia. NS-018 is a highly active JAK2 inhibitor, with an IC50 of 0.72 nM, 46-, 54-, and 31-fold selectivity for JAK2 over JAK1 (IC50, 33 nM), JAK3 (IC50, 39 nM), and Tyk2 (IC50, 22 nM). NS-018 also inhibits Src-family kinases, especially SRC and FYN, and weakly inhibits ABL and FLT3 with 45- and 90-fold selectivity for JAK2, respectively. NS-018 shows potent inhibitory activity against cell lines JAK2V617F or MPLW515L mutations or the TEL-JAK2 fusion gene.