JAK/STAT signaling

Nimbolide, a triterpenoid derived from neem leaves and flowers, is a natural product and a CDK4/CDK6/NF-κB inhibitor that inhibits multiple signaling pathways including Wnt and PI3K-Akt, possesses antitumor activity, and can induce tumor cell apoptosis.

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.

Osunprotafib (ABBV-CLS-484) hydrochloride is an orally active, selective inhibitor targeting the active sites of PTPN1 (IC50: 2.5 nM) and PTPN2 (IC50: 1.8 nM). It shows 6-8 times weaker activity towards PTPN9 and no detectable activity against SHP-1 or SHP-2. This compound enhances the sensitivity of human cancer cell lines to IFNγ. By boosting JAK-STAT signaling and reducing T cell dysfunction, Osunprotafib hydrochloride exhibits potent antitumor immunity.

PTPN2/1-IN-4 (Compound WS35) is an orally active dual inhibitor of PTPN1 and PTPN2, with IC50 values of 12.8 nM and 5.8 nM, respectively. It modulates the IFNγ-JAK-STAT signaling pathway and significantly enhances CD8+ T cell tumor infiltration. PTPN2/1-IN-4 demonstrates potent anticancer activity, effectively inhibiting tumor growth in the B16-OVA syngeneic mouse model both as a monotherapy and in combination with anti-PD-1 antibody treatment.

JAK2-IN-18 (Compound example1) is a selective JAK2 inhibitor. It effectively inhibits the JAK-STAT signaling pathway, with an IC50 value of less than 100 nM for pSTAT5 in HEL9217 cells. JAK2-IN-18 suppresses the proliferation of abnormally proliferating myeloid cells and is useful in research on myeloproliferative disorders, such as essential thrombocythemia.

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

2,4,5-Trimethoxybenzoic acid (Asaronic acid) is a natural product that inhibits M1 macrophage phenotype-induced inflammatory responses and suppresses TLR4/IL-6-mediated activation of NF-κB and JAK-STAT signaling pathways.

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].

Clazakizumab is a humanized monoclonal antibody targeting human interleukin -6(IL-6) with high affinity. By directly binding IL-6 ligand, it blocks its interaction with IL-6 receptor (IL-6α) and signal co-receptor gp130, thus inhibiting the activation of downstream JAK/STAT signaling pathway and weakening the inflammatory response. Clazakizumab can be used in the study of psoriasis arthritis and antibody-mediated organ transplant rejection.

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].

Frevecitinibum is a Janus kinase (JAK) inhibitor with activity against multiple JAK isoforms, including JAK1, JAK2, JAK3, and TYK2, thereby suppressing activation of the JAK-STAT signaling pathway. By modulating inflammatory cytokine signaling, Frevecitinibum has potential applications in research on respiratory inflammatory models such as asthma and Chronic Obstructive Pulmonary Disease.

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.

Anti-IFNAR1 Antibody (Anifrolumab) is a humanized IgG1 kappa monoclonal antibody targeting the type I interferon receptor subunit 1 (IFNAR1). This product specifically binds to IFNAR1, blocking the interaction of all type I interferons (including all subtypes of IFN-alpha, IFN-beta, and IFN-omega) with the receptor complex. This inhibition blocks the activation of the downstream JAK/STAT signaling pathway, reduces the expression of interferon-stimulated genes (ISGs), and suppresses type I interferon-mediated immune responses.

MEDI-2045 is a humanized monoclonal antibody targeting the interleukin-4 receptor alpha subunit (IL-4Ra). IL-4Ra is a pivotal receptor driving Type 2 inflammation, serving as an essential component of the shared receptor complexes for both IL-4 and IL-13. By specifically binding to IL-4Ra, this antibody dually blocks IL-4 and IL-13 signaling, thereby inhibiting the downstream JAK-STAT signaling pathway. This mechanism significantly attenuates inflammation involved in Th2 cell activation, B-cell class switching to IgE, and eosinophil recruitment, making it a critical tool for immunological research in asthma, atopic dermatitis, and other allergic diseases.

Anti-IL-20Ra Antibody is a highly specialized monoclonal antibody target the human interleukin-20 receptor α subunit with high affinity and selectivity, inhibition of ligand-induced signaling through the JAK-STAT pathway across various preclinical experimental models to modulate keratinocyte proliferation and inflammatory gene expression.

Brevilin A (Standard) is a reference standard for research and analysis in studies involving Brevilin A. 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