scholarly journals Optimization of a “bump-and-hole” approach to allele-selective BET bromodomain inhibition

2018 ◽  
Vol 9 (9) ◽  
pp. 2452-2468 ◽  
Author(s):  
A. C. Runcie ◽  
M. Zengerle ◽  
K.-H. Chan ◽  
A. Testa ◽  
L. van Beurden ◽  
...  
Keyword(s):  
Chemical Genetics ◽  
Selective Inhibition ◽  
Specific Chemical ◽  
Allele Specific

Allele-specific chemical genetics enables selective inhibition within families of highly-conserved proteins.

Fusion Protein Ompc-CD154 Inhibits Proliferation and Induces Apoptosis in B-NHL Cell Lines By a Mechanism That Involves MAPK P38 and TRAF2 Activation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5306-5306
Author(s):  
Gerardo Pantoja-Escobar ◽  
Laura Romo-Dorantes ◽  
Mario Morales-Martinez ◽  
Gabriel G Vega ◽  
Otoniel Martinez-Maza ◽  
...  
Keyword(s):  
Immune Response ◽  
Fusion Protein ◽  
Cell Lines ◽  
Conflicts Of Interest ◽  
Raji Cell ◽  
Selective Inhibition ◽  
Specific Chemical ◽  
Inhibition Of Proliferation ◽  
P38 Inhibitor

Abstract CD40 is a member of the TNF super family, which is expressed mainly in B cells, dendritic cells and macrophages, and the interaction with its ligand CD154 is essential for the development of the immune response. The activation or selective inhibition of this pathway is part of various therapeutic strategies for the treatment of diseases with inflammatory or immune origin, as well as various types of tumors. The fusion protein OmpC-CD154 expresses 10 amino acids of CD154 (Ser149-Trp140) and is capable of binding to CD40, inducing apoptosis and inhibiting proliferation in NHL cell lines. In this study we demonstrate that the fusion protein OmpC-CD154 induced apoptosis and inhibition of proliferation in several B-NHL cell lines. In addition, we analyzed the mechanisms involved in the induction of apoptosis and the inhibition of proliferation. Our results by Western blot demonstrate that OmpC-CD154 induced degradation of Bcl-6 by a MAPK p38 activation dependent mechanism. Pre-treatment of Ramos and Raji cell lines with a specific chemical p38 inhibitor reverted the effect of OmpC-CD154 in proliferation. Our results showed that the fusion protein can also inhibit the constitutive activation of both the canonical and non-canonical NF-kB pathways, and this inhibition was associated with the activation of the TRAFs pathway, as it promotes TRAF2 phosphorylation, and the decreasing of the expression of TRAF3. All these effects were greater than those observed with recombinant human CD154 on B-NHL cell lines. The present findings establish that a CD154 peptide fused with a protein exhibits significant cytotoxicity on B-NHL cells. Current studies are evaluating fusion proteins with CD154 peptide that are not antigenic in vivo and that have significant anti-tumor effects, both direct and on the host immune response, with minimal toxicity. Disclosures No relevant conflicts of interest to declare.

Allele-Specific Chemical Rescue of Histone Demethylases Using Abiotic Cofactors

2021 ◽  
Author(s):  
Valerie Scott ◽  
Debasis Dey ◽  
Jordan Kuwik ◽  
Kathryn Hinkelman ◽  
Megan Waldman ◽  
...  
Keyword(s):  
Histone Demethylases ◽  
Specific Chemical ◽  
Chemical Rescue ◽  
Allele Specific

scholarly journals Selective inhibition of PARP10 using a chemical genetics strategy

2015 ◽  
Vol 25 (21) ◽  
pp. 4770-4773 ◽  
Author(s):  
Rory K. Morgan ◽  
Ian Carter-O’Connell ◽  
Michael S. Cohen
Keyword(s):  
Chemical Genetics ◽  
Selective Inhibition

Stroma-derived factor 1alpha induces a selective inhibition of human erythroid development via the functional upregulation of Fas/CD95 ligand

2000 ◽  
Vol 111 (2) ◽  
pp. 432-440 ◽  
Author(s):  
Davide Gibellini ◽  
Alessandra Bassini ◽  
Maria Carla Re ◽  
Cristina Ponti ◽  
Sebastiano Miscia ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Cd95 Ligand ◽  
Erythroid Development

Increased response preparation overshadows neurophysiological evidence of proactive selective inhibition.

2018 ◽  
Vol 11 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Neil M. Drummond ◽  
Erin K. Cressman ◽  
Anthony N. Carlsen
Keyword(s):  
Selective Inhibition ◽  
Response Preparation

Selective inhibition of chemokine CCL2/MCP-1 reduces experimental pulmonary hypertension

Pneumologie ◽  
2013 ◽  
Vol 67 (05) ◽  
Author(s):  
D Kosanovic ◽  
BK Dahal ◽  
C Vroom ◽  
E Bieniek ◽  
H Ardeschir Ghofrani ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Selective Inhibition
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