AZD1480

In addition, we added the JAK2 inhibitor AZD1480 to explore the regulation of OTUB1 for JAK2/STAT1 pathway in GBM... Our study reveals a novel mechanism by which OTUB1 inhibits the JAK2/STAT1 signaling pathway. This contributes to a better understanding of OTUB1's role in GBM and provides a potential avenue for targeted therapeutic intervention.

VSIG4 suppresses oxidative stress, mitochondrial dysfunction, and inflammation by activating the JAK2/STAT3 pathway, which may be helpful in attenuating PD progression.

JAK2 inhibitor, AZD1480 exhibited a dose-dependent inhibition of the LIF-induced Gd-IgA1 overproduction...In summary, IgAN cells exhibit LIF-mediated overproduction of Gd-IgA1 due to abnormal signaling. JAK2 inhibitors can counter these LIF-induced effects and block Gd-IgA1 synthesis in IgAN.

Our studies discovered that lipids deposited in HDRR-LCCs were due to endogenous de novo fatty acids synthesis and exogenous lipids uptake. JAK2/p-TAT3/FASN could be used as promising targets for radiotherapy sensitization. Our study provided a new theoretical basis for studying the mechanism of radiation resistance in lung cancer.

Blocking STAT3 signaling with the JAK1/2 inhibitor AZD1480 restored PD-L1 blockade in pDCs and was associated with improved reduction of tumor burden...Our study shows that the presence of ADAs is associated with lack of antitumor responses to ant-PD-L1 blockade in a preclinical model of prostate cancer and provides additional data that will improve our understanding of ADAs against immune checkpoint inhibitors. This study also offers an approach to monitor ADA development and a platform to investigate novel approaches to target ADAs.

These results demonstrated that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. Our findings may inspire new strategies for HCC prevention and therapy.

IVM accelerates autophagic death of glioma cells by inhibiting glycolysis through blocking GLUT4 mediated JAK/STAT signaling pathway activation.

Taken together, our results suggest that IL4Rα and IL13Rα1 might be involved in the development of human gallbladder cancer cells and IL4Rα and IL13Rα1 complex/JAK2 signaling pathway could be efficient therapeutic targets for gallbladder cancer treatment.

Furthermore, AZD1480 (a JAK inhibitor) and MOAE inhibited the proliferation and migration of A549 cells and induced cell apoptosis, and the effects of MOAE and AZD1480 were not additive. These results indicated that MOAE inhibits the proliferation and migration of A549 cells and induces apoptosis and cell cycle arrest through a mechanism that is related to the inhibition of JAK2/STAT3 pathway activation. Thus, this extract has potential for preventing and treating lung cancer.

Here, we investigate the associations between the treatment pairings of PD-L1 antibody (aPD-L1, clone D265A, mouse/IgG1 kappa) blockade and the JAK1/2 inhibitor AZD1480 with ADT in mouse Pten-deficient prostate cancer and fecal gut microbiomes...Functionally, enrichments in fatty acid biosynthesis/metabolism, tetracycline biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and glycolysis/gluconeogenesis were revealed in responders whereas lipopolysaccharide biosynthesis, glycosaminoglycan degradation, fructose and mannose metabolism, histidine metabolism, glyoxylate and dicarboxylate metabolism, and the citrate cycle (TCA) were enriched in low responders. This study provides insight into the complex interactions between gut microbiota and cancer-burdened hosts, and reveals associations between gut microbial composition and treatment responses to androgen deprivation, immune modulation via JAK1/2 inhibition and PD-L1 blockade in a mouse model of Pten-deficient prostate cancer.

We show that both cucurbitacins decrease viability and cause apoptosis in these cell lines, although HuT-78 was more affected than SeAx (IC of 17.38 versus 22.01 μM for cucurbitacin E and 13.36 versus 24.47 μM for cucurbitacin I)...Furthermore, while JAK2 inhibition leads to decreased viability in SeAx cells (IC of 9.98 and 29.15 μM for AZD1480 and ruxolitinib respectively), both JAK1 and JAK3 do not...Nevertheless, a role of STAT5 and JAK2 cannot be excluded and should be explored further. This knowledge could contribute to the development of effective therapies for CTCL and other malignancies involving dysfunction of the JAK/STAT pathway.

Furthermore, treatment of JAK2 clinical medicine AZD1480 to ESCC cells showed similar tendency with Lico B. Thus, JAK2 downstream signaling proteins phosphorylation of STAT3 at Y705 and S727 as well as STAT3 target protein Mcl-1 expression was decreased with treatment of Lico B. Our results suggest that Lico B inhibits ESCC cell growth, arrests cell cycle and induces apoptosis, revealing the underlying mechanism involved in JAK2/STAT3 signaling pathways after Lico B treatment. It might provide potential role of Lico B in the treatment of ESCC.

Intact tumor bearing conditional Pten-knockout were treated for four weeks with an a-PD-L1 blocking antibody (clone D265A, mouse/IgG1 kappa) and/or the JAK1/2 inhibitor, AZD1480...The efficacy of the PJ>AD treatment combination was further tested and confirmed in a subcutaneous syngeneic allograft model using mice grafted with tumor blocks from Pten-deficient castration-resistant prostate cancer tumors. Together these results indicate that pretreatment with combined PD-L1/JAK blockade can decrease the immunosuppressive effects of androgen withdrawal and have the potential to restore antitumor immune activity in Pten-deficient prostate cancer.

For this we utilize 16S rDNA amplicon sequencing to profile the fecal microbiota (proximal and distal colon) of normal wildtype (WT) and tumor bearing conditional Pten-knockout (KO) mice treated for four weeks with the JAK1/2 inhibitor AZD1480 alone or in combination with orchidectomy...Using this approach, we have identified clusters of highly correlated taxa in the context of poorly inflamed and inflamed prostate tumors. Our findings show that systemic anticancer therapies can modify host microbiomes and provides insights into interactions between tumor, host microbiomes and immune modulating cancer therapies.

Targeted inhibition of ERK and JAK2/STAT5 signaling by SCH772984 and AZD1480, respectively, confirmed their roles in resistance to gilteritinib and CUDC-907 monotherapies, respectively. Cooperative inhibition of the PI3K-AKT, JAK-STAT, and RAS-RAF pathways, as well as upregulation of Bim/downregulation of Mcl-1 all appear to contribute to this observed antileukemic synergy. Our cell line-derived xenograft mouse model provides strong evidence of in vivo efficacy and robust grounds for clinical translation of this therapeutic combination.