JAK/STAT signaling

Nimbolide suppresses CDK4 CDK6 kinase activity. Nimbolide inhibits the NF-κB, Wnt, PI3K-Akt, MAPK, and JAK-STAT signaling pathways. Nimbolide causes apoptosis through the inactivation of NF-κB. Nimbolide is a triterpene derived from the leaves and flowers

Osunprotafib (ABBV-CLS-484) is a potent, orally bioavailable PTP1B PTPN2 inhibitor in clinical trials for solid tumors. [1] Osunprotafib (ABBV-CLS-484) stimulates the tumor microenvironment and promotes natural killer cell and CD8 T cell function and enhances T cell anti-tumor immunity by enhancing JAK-STAT signaling and reducing T cell dysfunction. [2]

Momelotinib (LM-1149) is an orally bioavailable small-molecule inhibitor of Janus kinases 1 and 2 (JAK1 2) with IC50 of 11 nM 18 nM. JAK1 2 inhibitor CYT387 competes with JAK1 2 for ATP binding, which may result in inhibition of JAK1 2 activation, inhibition of the JAK-STAT signaling pathway, and so the induction of apoptosis and a reduction of tumor cell proliferation in JAK1 2-expressing tumor cells.

DualCathepsinL JAK-IN-1 (Compound A8) serves as a dual inhibitor of Cathepsin L (CTSL) and JAK, exhibiting IC50 values of 0.68 μM for CTSL and 337.1 nM, 5.251 nM, 27.29 nM, and 172.6 nM for JAK1 2 3 and TYK2, respectively. This compound effectively prevents the activation of MAPK, NF-κB, and JAK STAT signaling pathways, leading to significant anti-inflammatory therapeutic effects. DualCathepsinL JAK-IN-1 is applicable in research on acute lung injury (ALI).

LNK01004 is a JAK inhibitor that exhibits potent inhibitory effects on JAK1 (IC50: 10 nM), JAK2 (IC50: ＜0.51 nM), and TYK2 (IC50: 1.0 nM). It can concurrently inhibit multiple cytokine-induced p-STAT signaling pathways and is applicable for research on diseases such as atopic dermatitis.

SD-1029 is a JAK2 inhibitor and a novel Stat3 activation inhibitor that inhibits Stat3 phosphorylation and JAK-STAT signaling.

BRD0476 is a suppressor of pancreatic β-cell apoptosis. BRD0476 inhibits interferon-gamma (IFN-γ)-induced Janus kinase 2 (JAK2) and signal transducer and activation of transcription 1 (STAT1) signaling to promote β-cell survival. BRD0476 inhibits JAK-STAT

Brevilin A is a sesquiterpene lactone isolated from Centipeda minima, inhibits janus kinase activity and blocks STAT3 signaling in cancer cells with anti-tumor activity. Brevilin A is a selective inhibitor of JAK-STAT signal pathway by attenuating the JAKs activity and blocking STAT3 signaling (IC50 = 10.6 μM) in Cancer Cells.Brevilin A induces apoptosis and autophagy via mitochondrial pathway and PI3K AKT mTOR inactivation in colon adenocarcinoma cell CT26.antitumour

INCB16562 is a novel, selective, and orally bioavailable small-molecule inhibitor of JAK1 and JAK2 markedly selective over JAK3. Treatment of myeloma cells with INCB16562 potently inhibited interleukin-6 (IL-6)-induced phosphorylation of STAT3. INCB16562 abrogated the protective effects of recombinant cytokines or bone marrow stromal cells and sensitized myeloma cells to cell death by exposure to dexamethasone, melphalan, or bortezomib. Oral administration of INCB16562 antagonized the growth of myeloma xenografts in mice and enhanced the antitumor activity of relevant agents in combination studies. INCB16562 is a potent JAK1 2 inhibitor and that mitigation of JAK STAT signaling by targeting JAK1 and JAK2 will be beneficial in the treatment of myeloma patients, particularly in combination with other agents. ( source: Neoplasia. 2010 Jan;12(1):28-38. ).

AUH-6-96 is an inhibitor of JAK STAT signaling, inhibiting both constitutive and interleukin-6-induced STAT3 phosphorylation, selectively affecting cell viability only of cancer cells harboring aberrant JAK STAT signaling.

HAT-SIL-TG-1&AT, a hypoxia-activated prodrug, functions as a Janus tyrosine kinase (JAK) inhibitor demonstrating antitumor effects by inhibiting JAK-STAT signaling within tumor tissues. It also suppresses the proliferation of HEL cells and downregulates phosphorylated STAT3 5 in hypoxic conditions.

5-epi-Arvestonate A, a sesquiterpenoid extracted from Seriphidium transiliense whole plants, enhances melanogenic production by stimulating MITF and tyrosinase family gene transcription. Additionally, it suppresses IFN-γ-chemokine expression via the JAK STAT signaling pathway in HaCaT cells [1].

JE-133, an optically active isochromane-2H-chromene conjugate, displays both antioxidant and anti-inflammatory properties. As a neuroprotective agent, it effectively counters neuronal oxidative damage through modulation of the PI3K Akt and MAPK signaling pathways. Additionally, JE-133 can suppress lipopolysaccharide (LPS)-induced neuroinflammation by influencing the JAK STAT and Nrf2 signaling pathways [1] [2].

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.