P1, N=48, Not yet recruiting, Washington University School of Medicine | Trial completion date: Dec 2031 --> Apr 2032 | Initiation date: Oct 2025 --> Feb 2026 | Trial primary completion date: Jan 2030 --> May 2030
8 days ago
Trial completion date • Trial initiation date • Trial primary completion date
Using an innovative collagen gel implantation model, we demonstrate that loss of MYD88 in CAFs enhances T cell infiltration and suppresses tumor growth. Combining MYD88 inhibition with immune checkpoint blockade significantly reduces tumor size and enhances antitumor immune responses, underscoring its potential as a therapeutic target in PDAC.
3 months ago
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
In this article, we describe the development of a highly potent and selective IRAK4 lead compound 5e, starting from Astellas AS2444697 (1a). The work includes identification of the pyrazole-pyridine substituent in compound 1g, binding towards the gatekeeper region of IRAK4, followed by a structure-guided scaffold hybridization that led to 5a. Subsequent optimization of substituents of the indazole scaffold yielded 5e, which exhibits a 10-fold improvement in IRAK4 cell potency and higher off-target selectivity compared to AS244697 (1a).