jak2 (v617f)

Fedratinib (TG-101348) (TG101348) is an ATP-competitive inhibitor of JAK2 (IC50: 3 nM) with significantly less potent activity against JAK3.

Fedratinib hydrochloride hydrate (SAR 302503 hydrochloride hydrate) is a potent, selective, ATP-competitive and orally active JAK2 inhibitor.

LY2784544(Gandotinib (LY2784544)) is a potent JAK2 inhibitor (IC50: 3 nM), effective in JAK2V617F(Ki: 0.245 nM). The selectivity is higher 8- and 20-fold than JAK1 and JAK3.

JAK2 Inhibitor V (JAK2 Inhibitor V Z3) is a novel specific inhibitor of Jak2, inhibiting Jak2-V617F and Jak2-WT autophosphorylation in a dose-dependent manner.

Pacritinib (SB1518) (SB1518) is an effective and specific inhibitor of JAK2 and FLT3 (IC50: 23/22 nM, in cell-free assays).

JAK2-IN-10 is a potent inhibitor of JAK2v617f, with an IC50 value of ≤10 nM.

ON044580 is an effective non-ATP-competitive inhibitor of JAK2, characterized as an α-benzoylstyrylbenzyl thioether. It exhibits IC50 values of 1.23 μM for wild type JAK2 and 1.09 μM for the V617F mutation. The compound inhibits JAK2 kinase activity by binding to the STAT-5 binding domain or the allosteric site of JAK2. In JAK2V617F-positive leukemia cells, ON044580 suppresses proliferation and induces apoptosis in Imatinib-resistant chronic myeloid leukemia (CML) cells. It also inhibits both wild type and T315I mutant forms of the BCR-ABL kinase. ON044580 is used in research for myeloproliferative diseases characterized by abnormal JAK/STAT signaling.

Erlotinib (NSC-718781) is an EGFR inhibitor (IC50: 2 nM). It is used for the treatment of non-small cell lung cancer.

JAK2-IN-11 is a JAK2 kinase inhibitor with potent antitumor activity, exhibiting an IC50 of ≤10 nM against JH2 BIND WT/V617F. This compound effectively suppresses tumor growth.

PROTAC JAK2 degrader-1 (Compound 10i) is a JAK2 PROTAC degrader with a DC50 of 27.35 nM against JAK2V617F. It facilitates the ubiquitination and degradation of JAK2. This compound also inhibits the phosphorylation of JAK2, STAT3, and STAT5, and is applicable in the study of myeloproliferative neoplasms.

WWQ-03-012 is a selective inhibitor of deSUMOylating isopeptidase DESI2, with an IC50 of 47.3 μM. It induces ubiquitination-proteasome degradation of JAK2-V617F without significantly affecting wild-type JAK2. This compound can disrupt the JAK2-STAT3/5 signaling pathway, inhibit cell proliferation, and induce apoptosis. When used in combination with Ruxolitinib, WWQ-03-012 demonstrates a synergistic effect, enhancing cytotoxicity against JAK2 mutant cells. It is applicable in cancer research, specifically in studying myeloproliferative neoplasms.

XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, 100 fold selectivity over JAK1.

JAK2 inhibitor (IC50 = 397 nM). Also inhibits STAT3 and STAT5 phosphorylation. Inhibits cell growth and induces apoptosis in cells expressing the JAK2V617F mutation. Manshouri et al (2011) Bone marrow stroma-secreted cytokines protect JAK2(V617F)-mutated cells from the effects of a JAK2 inhibitor. Cancer Res. 71 3831 PMID:21512135 |Quintás-Cardama et al (2011) Preclinical characterization of atiprimod, a novel JAK2 AND JAK3 inhibitor. Invest.New Drugs 29 818 PMID:20372971

JAK2-IN-7, a selective inhibitor targeting Janus Kinase 2 (JAK2), exhibits inhibitory concentrations (IC50) of 3 nM for JAK2, 11.7 nM for SET-2 cells, and 41 nM for Ba/F3 V617F cells, indicative of its potency and selectivity. This compound demonstrates more than 14-fold selectivity against JAK1, JAK3, and FLT3, underlining its specificity. JAK2-IN-7 effectively induces cell cycle arrest at the G0/G1 phase and promotes apoptosis in tumor cells, manifesting significant antitumor activities [1].

NVP-BSK805 trihydrochloride is a potent ATP-competitive inhibitor of JAK2, exhibiting IC50 values of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM against JAK2 JH1, JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively.

NVP-BSK805 (BSK 805) is an ATP-competitive JAK2 inhibitor.

JAK-IN-21 is a selective and potent JAK inhibitor that inhibits JAK1, JAK2, J2V617F and TYK2 with IC50 values of 1.73, 2.04, 109 and 62.9 nM, respectively.

Pacritinib hydrochloride is a potent inhibitor of wild-type JAK2 (IC50: 23 nM) and the JAK2V617F mutant (IC50: 19 nM), and can be used in the study of acute myeloid leukaemia (AML) and myelofibrosis (MF).

AC430 is a potent and specific small molecule inhibitor of janus kinase 2 (JAK2), which has been implicated as a target for therapy in both oncology and autoimmune disease. AC430 is currently being developed by Ambit. In preclinical studies, AC430 has exhibited potency against JAK2 and V617F mutated JAK2 in cell-based models that is at least equivalent to, and in most cases superior to, competing JAK2 inhibitors. In preclinical oncology and autoimmune models, AC430 is well tolerated and has significant efficacy at oral doses as low as 10 mg/kg/day.

ZT55, an orally active, highly-selective JAK2 inhibitor with an IC50 of 0.031 μM, inhibits proliferation of JAK2 V617F-expressing HEL cell lines, induces apoptosis and cycle arrest, and effectively inhibits HEL xenograft tumor growth in mice models. Suitable for studies on myeloproliferative neoplasms, polycythemia vera, and primary thrombocythemia, ZT55 offers promising applications.

Pacritinib (SB1518) citrate effectively inhibits wild-type JAK2 (IC 50 =23 nM) and the JAK2 V617F mutant (IC 50 =19 nM). It also targets FLT3 (IC 50 =22 nM) and the FLT3 D835Y mutant (IC 50 =6 nM). This compound is utilized in the study of acute myeloid leukemia (AML) and myelofibrosis (MF) [1] [2] [3].