JAK3 Inhibitor

Ruxolitinib (INCB18424) is an orally active and selective JAK1/2 inhibitor with IC₅₀s of 3.3 nM and 2.8 nM in cell-free assays, and has 130-fold selectivity for JAK1/2 over JAK3. Ruxolitinib induces autophagy and kills tumor cells through toxic mitophagy.

Tofacitinib is an orally available JAK3/2/1 inhibitor with IC₅₀s of 1, 20, and 112 nM, respectively.

Upadacitinib (ABT-494) is a potent, orally active and selective Janus kinase 1 (JAK1) inhibitor (IC₅₀=43 nM). Upadacitinib (ABT-494) displays approximately 74 fold selective for JAK1 over JAK2 (200 nM) in cellular assays dependent on specific, relevant cytokines. Upadacitinib (ABT-494) can be used for several autoimmune disorders research.

Baricitinib (LY3009104; INCB028050) is a selective and orally bioavailable JAK1 and JAK2 inhibitor with IC₅₀s of 5.9 nM and 5.7 nM, respectively.

Ruxolitinib phosphate (INCB018424 phosphate) is a potent JAK1/2 inhibitor with IC₅₀s of 3.3 nM/2.8 nM, respectively, showing more than 130-fold selectivity over JAK3.

JAK3-IN-20 is a selective and orally active JAK3 inhibitor with an IC₅₀ of 0.7473 nM. JAK3-IN-20 forms a covalent bond with JAK3 Cys909, outcompetes ATP for catalytic site binding, and blocks JAK-STAT pathway activation. JAK3-IN-20 inhibits migration, proliferation, and tumor growth of Bortezomib (HY-10227)-resistant cancer cells. JAK3-IN-20 induces dose-dependent apoptosis. JAK3-IN-20 can be used for the research of Bortezomib-resistant multiple myeloma.

Tofacitinib citrate is an orally available JAK3/2/1 inhibitor with IC₅₀s of 1, 20, and 112 nM, respectively. Tofacitinib citrate has antibacterial, antifungal and antiviral activities.

Ritlecitinib (PF-06651600) is a highly selective, orally active, irreversible covalent JAK3 inhibitor (IC₅₀=33 nM) without inhibitory activity towards JAK1, JAK2, and TYK2 (IC₅₀ >10 μ M). Ritlecitinib rapidly inactivates the JAK3 kinase, and blocks signaling and downstream STAT phosphorylation mediated by common gamma chain cytokines such as IL-2 and IL-15. Ritlecitinib can inhibit Th1/Th17 cell differentiation and function, and effectively suppress preclinical animal models such as alopecia areata, adjuvant-induced arthritis (AIA), and experimental autoimmune encephalomyelitis (EAE).

Pacritinib (SB1518) is a potent inhibitor of both wild-type JAK2 (IC₅₀=23 nM) and JAK2^V617F mutant (IC₅₀=19 nM). Pacritinib also inhibits FLT3 (IC₅₀=22 nM) and its mutant FLT3^D835Y (IC₅₀=6 nM).

Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC₅₀a of 11 nM and 18 nM,respectively. CYT387 shows much less activity against JAK3.

Filgotinib (GLPG0634) is a selective, orally available JAK1 inhibitor with anti-inflammatory and antiviral activities. Filgotinib can effectively inhibit the activities of JAK1, JAK2, JAK3 and TYK2 with IC₅₀ values of 10 nM, 28 nM, 810 nM and 116 nM, respectively. Filgotinib also inhibits HIV-1 driven gene transcription and reduces proliferation of HIV-1 infected cells. Filgotinib can be used in the study of rheumatoid arthritis and inflammatory bowel disease.

Peficitinib (ASP015K) is an orally active JAK inhibitor, with IC₅₀s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.

Brepocitinib (PF-06700841) is a potent dual Janus kinase 1 (JAK1) and TYK2 inhibitor with IC₅₀s of 17 nM and 23 nM, respectively. Brepocitinib also inhibits JAK2 and JAK3 with IC₅₀s of 77 nM and 6.49 μM, respectively.

Baricitinib phosphate (LY3009104 phosphate; INCB028050 phosphate) is a selective orally bioavailable JAK1/JAK2 inhibitor with IC₅₀ of 5.9 nM and 5.7 nM, respectively.

AT9283 is a multi-targeted kinase inhibitor with potent activity against Aurora A/B, JAK2/3, Abl (T315I) and Flt3 (IC₅₀s ranging from 1 to 30 nM). AT9283 inhibits growth and survival of multiple solid tumors in vitro and in vivo.

Pyridone 6 is a pan-JAK inhibitor, which potently inhibits the JAK kinase family, with IC₅₀s of 1 nM for JAK2 and TYK2, 5 nM for JAK3, and 15 nM for JAK1, while displaying significantly weaker affinities (130 nM to >10 mM) for other protein tyrosine kinases.

Cerdulatinib (PRT062070) is a selective Tyk2 inhibitor with an IC₅₀ of 0.5 nM. Cerdulatinib (PRT062070) also is a dual JAK and SYK inhibitor with IC₅₀s of 12, 6, 8 and 32 for JAK1, 2, 3 and SYK, respectively.

Delgocitinib (JTE-052) is a specific JAK inhibitor with IC₅₀s of 2.8, 2.6, 13 and 58 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.

Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC₅₀ of 3 nM. Gandotinib (LY2784544) also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC₅₀ of 4, 25, 32, 44, and 95 nM.

BD750, an effective immunosuppressant and a JAK3/STAT5 inhibitor, inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation, with IC₅₀ values of 1.5 μM and 1.1 μM in mouse and human T cells, respectively.