pci-32765 and Tuberculosis

pci-32765 has been researched along with Tuberculosis* in 2 studies

Other Studies

2 other study(ies) available for pci-32765 and Tuberculosis

Article	Year
Ibrutinib suppresses intracellular mycobacterium tuberculosis growth by inducing macrophage autophagy. The Journal of infection, 2020, Volume: 80, Issue:6 Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. The host-directed therapy is a promising strategy for TB treatment that synergize with anti-TB treatment drugs. In this study, we found that the anti-chronic lymphocytic leukemia drug, ibrutinib, inhibited the growth of intracellular Mtb in human macrophages. Mechanisms studies showed that ibrutinib treatment significantly decreased p62 and increased LC3b proteins in Mtb infected macrophages. In addition, ibrutinib increased LC3b colocalization with intracellular Mtb and auto-lysosome fusion. Furthermore, inhibition of autophagy by using siRNA targeting ATG7 abolished the effect of ibrutinib-mediated suppression of intracellular Mtb. Next, we found that ibrutinib induced autophagy was through inhibition of BTK/Akt/mTOR pathway. Finally, we confirmed that ibrutinib treatment significantly reduced Mtb load in mediastinal node and spleen of Mtb infected mice. In conclusion, our data suggest that ibrutinib is a potential host-directed therapy candidate against TB. Topics: Adenine; Animals; Autophagy; Macrophages; Mice; Mycobacterium tuberculosis; Piperidines; Tuberculosis	2020
Design and Synthesis of Novel Amino-triazine Analogues as Selective Bruton's Tyrosine Kinase Inhibitors for Treatment of Rheumatoid Arthritis. Journal of medicinal chemistry, 2018, 10-11, Volume: 61, Issue:19 Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of multiple diseases, such as B-cell malignances, asthma, and rheumatoid arthritis. A series of novel aminotriazines were identified as highly selective inhibitors of BTK by a scaffold-hopping approach. Subsequent SAR studies of this series using two conformationally different BTK proteins, an activated form of BTK and an unactivated form of BTK, led to the discovery of a highly selective BTK inhibitor, 4b. With significant efficacy in models in vivo and good ADME and safety profiles, 4b was advanced into preclinical studies. Topics: Agammaglobulinaemia Tyrosine Kinase; Animals; Antitubercular Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Drug Design; Male; Mice; Mice, Inbred DBA; Molecular Structure; Mycobacterium tuberculosis; Protein Kinase Inhibitors; Tuberculosis	2018

Article

Year

Ibrutinib suppresses intracellular mycobacterium tuberculosis growth by inducing macrophage autophagy.

The Journal of infection, 2020, Volume: 80, Issue:6

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. The host-directed therapy is a promising strategy for TB treatment that synergize with anti-TB treatment drugs. In this study, we found that the anti-chronic lymphocytic leukemia drug, ibrutinib, inhibited the growth of intracellular Mtb in human macrophages. Mechanisms studies showed that ibrutinib treatment significantly decreased p62 and increased LC3b proteins in Mtb infected macrophages. In addition, ibrutinib increased LC3b colocalization with intracellular Mtb and auto-lysosome fusion. Furthermore, inhibition of autophagy by using siRNA targeting ATG7 abolished the effect of ibrutinib-mediated suppression of intracellular Mtb. Next, we found that ibrutinib induced autophagy was through inhibition of BTK/Akt/mTOR pathway. Finally, we confirmed that ibrutinib treatment significantly reduced Mtb load in mediastinal node and spleen of Mtb infected mice. In conclusion, our data suggest that ibrutinib is a potential host-directed therapy candidate against TB.

Topics: Adenine; Animals; Autophagy; Macrophages; Mice; Mycobacterium tuberculosis; Piperidines; Tuberculosis

2020

Design and Synthesis of Novel Amino-triazine Analogues as Selective Bruton's Tyrosine Kinase Inhibitors for Treatment of Rheumatoid Arthritis.

Journal of medicinal chemistry, 2018, 10-11, Volume: 61, Issue:19

Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of multiple diseases, such as B-cell malignances, asthma, and rheumatoid arthritis. A series of novel aminotriazines were identified as highly selective inhibitors of BTK by a scaffold-hopping approach. Subsequent SAR studies of this series using two conformationally different BTK proteins, an activated form of BTK and an unactivated form of BTK, led to the discovery of a highly selective BTK inhibitor, 4b. With significant efficacy in models in vivo and good ADME and safety profiles, 4b was advanced into preclinical studies.

Topics: Agammaglobulinaemia Tyrosine Kinase; Animals; Antitubercular Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Drug Design; Male; Mice; Mice, Inbred DBA; Molecular Structure; Mycobacterium tuberculosis; Protein Kinase Inhibitors; Tuberculosis

2018