Products/Services Used | Details | Operation |
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Recombinant Antibody Services> | Continued REAGENT or RESOURCE SOURCE IDENTIFIER QVD-Oph Millipore Sigma 551476 Recombinant human TNFa R&D systems 210-TA-100 FLAG-RIPK1 1-294 (C34A C127A C233A C240A) Genscript N/A fluorescently-labeled ligand (14-(2-{[3-({2-{[4-(cyanomethyl)phenyl]amino}- 6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-4-pyrimidinyl}amino) propyl] amino}-2-oxoethyl)-16,16,18,18-tetramethyl-6,7,7a,8a,9,10,16,18- octahydrobenzo [2’,3’]indolizino[8’,7’:5 ,6 ]pyrano [3 ,2 :3,4]pyrido[1,2-a] indol-5-ium-2-sulfonate) 0 0 0 0 GSK N/A Critical Commercial Assays MILLIPLEX Human Cytokine 41-Plex kit MilliporeSigma Cat#: HCYTMAG-60K-PX41 Reaction Biology Kinase Assay Reaction Biology Corp Wild type kinase panel Cell Titre-Glo Luminescent Cell Viability Assay Promega G7573 Deposited Data X-ray crystalllography data, maps and structure coordinates: PDB This paper 6HHO https://www. | Get A Quote |
Pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance and immunotherapeutic resistance. We discovered upregulation of receptor-interacting serine/threonine protein kinase 1 (RIP1) in tumor-associated macrophages (TAMs) in PDA. To study its role in oncogenic progression, we developed a selective small-molecule RIP1 inhibitor with high in vivo exposure. Targeting RIP1 reprogrammed TAMs toward an MHCIIhiTNFα+IFNγ+ immunogenic phenotype in a STAT1-dependent manner. RIP1 inhibition in TAMs resulted in cytotoxic T cell activation and T helper cell differentiation toward a mixed Th1/Th17 phenotype, leading to tumor immunity in mice and in organotypic models of human PDA. Targeting RIP1 synerg... More