Discovery of INCB159020, an Orally Bioavailable KRAS G12D Inhibitor.

The inhibition of mutant KRAS proteins has emerged as a promising approach for treating KRAS-driven cancers, as evidenced by the clinical success of KRAS G12C inhibitors. KRAS G12D, the most common mutant, promises significant expansion of the addressable patient population; however, the reduced nucleophilicity of aspartate compared to cysteine poses significant challenges in balancing sufficient potency with ADME properties to support oral exposure. Herein, we describe the discovery of KRAS G12D inhibitor (), which achieves oral exposure in nonhuman primate (NHP).

The impact of transplant location on the gut microbiome and resistome in patients undergoing hematopoietic stem cell transplantation at home versus in the hospital.

Objectives: Home-based hematopoietic stem cell transplantation (HCT) is a novel approach that has the potential to improve outcomes, however, the impact of transplant location on the gut microbiome remains uncharacterized. We hypothesized that patients randomized to undergo home HCT would have higher gut taxonomic diversity and lower antimicrobial resistance (AMR) gene abundance compared to those undergoing standard hospital HCT.

Methods: We identified 28 patients enrolled in Phase II randomized trials of home (n=16) v.

Generating Biomedical Knowledge Graphs from Knowledge Bases, Registries, and Multiomic Data.

As large clinical and multiomics datasets and knowledge resources accumulate, they need to be transformed into computable and actionable information to support automated reasoning. These datasets range from laboratory experiment results to electronic health records (EHRs). Barriers to accessibility and sharing of such datasets include diversity of content, size and privacy.