JAK1 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.

Deucravacitinib (BMS-986165) is an orally active allosteric inhibitor of tyrosine kinase 2 (TYK2), with an IC₅₀ of 0.2 nM and a K_i of 0.02 nM against the JH2 domain of TYK2, and it exhibits selectivity over other JAK subtypes and most of the kinome. Deucravacitinib blocks IL-23, IL-12, p-STAT1/3 and Type I IFN signaling, and inhibits Th17/Th1-mediated psoriasis inflammation. Deucravacitinib can be used in research related to moderate-to-severe plaque psoriasis, inflammatory bowel disease and systemic lupus erythematosus.

RAI-20 (H018) is an orally active JAK1/JAK2 dual inhibitor (IC₅₀=15.1 and 22.7 nM). RAI-20 exhibits excellent pharmacokinetic properties, including plasma stability, systemic exposure, and a long half-life. In a collagen-induced arthritis rat model, RAI-20 shows significant anti-inflammatory and anti-arthritic activities, effectively reducing paw swelling volume and arthritis index. RAI-20 can be used for research on the pathogenesis of rheumatoid arthritis.

YYSW001 is a selective and orally acrive JAK1 inhibitor with an IC₅₀ of 6 nM and a Kd of 32.32 μM. YYSW001 blocks JAK1-dependent phosphorylation of STAT6, as well as IL-6-induced phosphorylation of STAT3. YYSW001 suppresses pro-inflammatory cytokine levels, reduces paw swelling, lowers clinical arthritis scores, alleviates joint damage and decreases bone loss. YYSW001 is applicable for the research of rheumatoid arthritis.

JAK1-IN-22 is a JAK1-selective inhibitor with an IC₅₀ of 1.84 μM. JAK1-IN-22 exerts no significant inhibitory effect on JAK2 and JAK3. JAK1-IN-22 can be used in the research of JAK1-related diseases such as asthma, alopecia areata, and type 1 diabetes.

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.

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.

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.

Abrocitinib (PF-04965842) is a potent, orally active and selective JAK1 inhibitor, with IC₅₀s of 29 and 803 nM for JAK1 and JAK2, respectively. Abrocitinib (PF-04965842) exhibits less active effect on TYK2 (IC₅₀, 1.253 μM), and inhibits phosphorylation of STAT1, STAT3 and STAT5 after stimulation. Effective in autoimmune disease.

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.

Itacitinib (INCB039110) is an orally active selective inhibitor of JAK1 with an IC₅₀ value of 2 nM for human JAK1. Itacitinib inhibits IFN-γ-mediated phosphorylation of STAT1 and downstream pro-inflammatory signaling pathways. Itacitinib reduces the frequency and number of splenic neutrophils in mouse models, downregulates the levels of pro-inflammatory cytokines and chemokines, and inhibits pro-inflammatory gene expression pathways. Itacitinib improves survival rate and clinical scores in mouse models of hemophagocytic lymphohistiocytosis (HLH), and also suppresses metastasis in NSCLC models with high Rab1A expression. Itacitinib can be used for research on hemophagocytic lymphohistiocytosis and non-small cell lung cancer.

AZD-1480 is an ATP-competitive inhibitor of JAK1 and JAK2 with IC₅₀s of 1.3 nM and <0.4 nM, respectively.

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.

Golidocitinib (AZD4205) is a selective JAK1 inhibitor, with an IC₅₀ of 73 nM, weakly inhibits JAK2 (IC₅₀>14.7 μM), and shows little inhibition on JAK3 (IC₅₀>30 μM).

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.