STAT5 Inhibitor

Ritlecitinib (PF-06651600) is a highly selective, orally active, irreversible covalent JAK3 inhibitor (IC₅₀=33 nM) without inhibitory activity towards JAK1, JAK2, and TYK2 (IC₅₀ >10 μ M). Ritlecitinib rapidly inactivates the JAK3 kinase, and blocks signaling and downstream STAT phosphorylation mediated by common gamma chain cytokines such as IL-2 and IL-15. Ritlecitinib can inhibit Th1/Th17 cell differentiation and function, and effectively suppress preclinical animal models such as alopecia areata, adjuvant-induced arthritis (AIA), and experimental autoimmune encephalomyelitis (EAE).

STAT5-IN-1 is a STAT5 inhibitor with an IC₅₀ of 47 μM for STAT5β isoform.

Pimozide is a dopamine receptor antagonist, with K_is of 1.4 nM, 2.5 nM and 588 nM for dopamine D2, D3 and D1 receptors, respectively, and also has affinity at α1-adrenoceptor, with a K_i of 39 nM; Pimozide also inhibits STAT3 and STAT5.

AC-4-130 is a potent STAT5 SH2 domain inhibitor. AC-4-130 directly binds to STAT5 and disrupts STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription. AC-4-130 induces cell cycle arrest and apoptosis in FLT3-ITD-driven leukemic cells. AC-4-130 has anti-cancer activity and can efficiently block pathological levels of STAT5 activity in acute myeloid leukemia (AML).

INCA033989 is a fully human IgG1 monoclonal antibody targeting mutCALR (K_D = 1.75 nM for mutCALR^del52; K_D = 6.78 nM for mutCALR^ins5). INCA033989 antagonizes mutCALR-driven signaling and proliferation. INCA033989 selectively inhibits pSTAT3/pSTAT5. INCA033989 prevents thrombocytosis and reduces the expansion of mutCALR-positive cells. INCA033989 is useful for research on myeloproliferative neoplasms .

TAVO101 is a humanized anti-TSLP antibody with an EC₅₀ of 0.19 nM against hTSLP. TAVO101 inhibits STAT5 activation and CCL17 release. TAVO101 carries Fc region mutations that enhance its binding to FcRn while reducing its binding to FcγRI, FcγRIIIA and C1q, thereby attenuating effector functions. TAVO101 reduces the levels of inflammatory markers, cell infiltration and histopathological damage in preclinical models of asthma, psoriasis and atopic dermatitis. TAVO101 can be used for research related to asthma, psoriasis and atopic dermatitis.

FLT3-IN-41 is a highly potent FLT3 inhibitor. The IC₅₀ values of FLT3-IN-41 against human FLT3-ITD and FLT3-WT are 3.16 nM and 294.7 nM, respectively. By binding to the ATP-binding pockets of FLT3-ITD and FLT3-WT and forming hydrogen bonds with hinge region residues and Phe830, FLT3-IN-41 inhibits the STAT5, Akt and Erk signaling pathways. FLT3-IN-41 induces G2/M phase arrest and promotes apoptosis in FLT3-ITD-positive acute myeloid leukemia cells, exhibiting significant antiproliferative activity. FLT3-IN-41 serves as a valuable tool for the study of acute myeloid leukemia.

SH-4-54 is a CNS-penetrant STAT inhibitor that binds to STAT3 and STAT5 with K_Ds of 300, 464 nM, respectively.

STAT4-IN-1 is an inhibitor of STAT4 with a K_i of 0.35 μM. STAT4-IN-1 is expected to be used in the research of autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and diabetes.

BD750, an effective immunosuppressant and a JAK3/STAT5 inhibitor, inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation, with IC₅₀ values of 1.5 μM and 1.1 μM in mouse and human T cells, respectively.

Stafia-1 is a potent STAT5a inhibitor (K _i=10.9 μM, IC₅₀=22.2 μM). Stafia-1 displays high selectivity over STAT5b and other STAT family members.

IST5-002, a potent Stat5a/b inhibitor, selectively inhibits transcriptional activity of Stat5a/b (IC₅₀s: 1.5 μM for Stat5a, 3.5 μM for Stat5b). IST5-002 inducs cell apoptotic and death of prostate cancer cells and chronic myeloid leukemia (CML) cells. IST5-002 can be used in the research of prostate cancer and chronic myeloid leukemia (CML).

Stafib-1 is the first selective inhibitor of the STAT5b SH2 domain, with a K_i of 44 nM and an IC₅₀ of 154 nM.

NSC-370284 is a selective inhibitor of ten-eleven translocation 1 (TET1) and 5-hydroxymethylcytosine (5hmC). NSC-370284 significantly inhibits the level of TET1 expression via targets STAT3/5.

STAT5-IN-2 is a STAT5 inhibitor, extracted from reference 1, example 17f. STAT5-IN-2 has potent antileukemic effect.

GMB-475 is a potent BCR-ABL1 PROTAC based on Von Hippel-Lindau (VHL). GMB-475 targets the nutmeg pocket of ABL1 in an ectopic manner and degrades BCR-ABL1 protein through the ubiquitin proteasome pathway. GMB-475 inhibits the proliferation of human K562 cells and mouse Ba/F3 cells, and is used for the study of chronic myeloid leukemia.

Cenisertib (AS-703569) is an ATP-competitive multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT, STAT5 and FLT3. Cenisertib induces major growth-inhibitory effects by blocking the activity of several different molecular targets in neoplastic mast cells (MC). Cenisertib inhibits tumor growth in xenograft models of pancreatic, breast, colon, ovarian, and lung tumors and leukemia.

AS2863619 free base is an orally active CDK8/19 inhibitor that also inhibits BMP2, MDA5 and RIG-I receptors. AS2863619 free base targets Stat5a-CDK8/19 to promote the differentiation of CD4⁺ T cells into regulatory T cells and induce FOXP3 expression, thereby restoring immune homeostasis and establishing transplant immune tolerance. AS2863619 free base also enhances the BMP2/SMAD signaling pathway to promote osteogenic differentiation and inhibit adipogenic differentiation. AS2863619 free base exerts osteoprotective effects by alleviating inflammation-induced impairment of osteogenic function and inducing neutrophil apoptosis (apoptosis). AS2863619 free base can be applied to research in related fields such as periodontitis-induced bone defects.

GSK2618960 is a human monoclonal antibody (mAb) targeting IL-7Ra/CD127. GSK2618960 inhibits IL-7-induced STAT5 phosphorylation. GSK2618960 enhances CD4 T cell proliferation response and increases CD83, CD86, and CD209 expression in PBMCs. GSK2618960 can be used for the research of autoimmune and allergic inflammatory diseases. Recommended isotype control: Human IgG1 kappa, Isotype Control (HY-P99001).

HODHBt (HOOBt) inhibits STAT5-SUMO interaction by blocking SUMOylation of phosphorylated STAT5. HODHBt enhances the magnitude of IL-15 signaling and significantly increases the natural killer (NK) cell cytotoxicity phenotype and function and the generation of cytokine-induced memory-like (CIML) natural killer (NK) cells. HODHBt can be used for research of HIV-infection and cancer.