JAK2 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.

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.

Fedratinib (TG-101348) is a potent, selective, ATP-competitive and orally active JAK2 inhibitor with IC₅₀s of 3 nM for both JAK2 and JAK2V617F kinase. Fedratinib shows 35- and 334-fold selectivity over JAK1 and JAK3, respectively. Fedratinib induces cancer cell apoptosis and has the potential for myeloproliferative disorders research.

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.

ARV-825 is a BET protein PROTAC degrader that recruits cereblon, and it targets BRD2, BRD3, and BRD4 for degradation via the ubiquitin-proteasome pathway. ARV-825 downregulates c-MYC, PLK1, MYCN, CDK4/6, JAK2, pSTAT3/5, PIM1, and Bcl-xL, upregulates p21 and p27, and modulates H3K27Ac-mediated transcription, the G2/M checkpoint, the Wnt/β-catenin pathway, and amino acid transport pathways. ARV-825 induces G1 phase cell cycle arrest, caspase 3/PARP-mediated apoptosis, DNA damage, and reactive oxygen species (ROS) production, reduces mitochondrial respiration, and simultaneously inhibits cell proliferation, clonogenic growth, and cell migration. ARV-825 is used in research on gastric cancer, leukemia, neuroblastoma, and cholangiocarcinoma.

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.

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).

WP1066 is an inhibitor of JAK2 and STAT3, and also shows effect on STAT5 and ERK1/2, without affecting JAK1 and JAK3. WP1066 can cross the blood-brain barrier[1][2][3][4].

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.

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.

CHZ868 is a type II JAK2 inhibitor with an IC₅₀ of 0.17 μM in EPOR JAK2 WT Ba/F3 cell.

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.

Cucurbitacin I is a natural selective inhibitor of JAK2/STAT3, with potent anti-cancer activity.

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.