Article

A structure-based modelling approach identifies effective drug combinations for RAS-mutant acute myeloid leukemia

2025-05-03

Abstract excerpt

Mutations activating RAS/RAF/MEK/ERK signaling are associated with poor outcome in acute myeloid leukemia (AML), but therapeutic targeting of this pathway is challenging. Here, we employ a structure-based, dynamic RAS pathway model to successfully predict RAF inhibitor (RAFi) combinations which synergistically suppress ERK signaling in RAS -mutant AML. Our in silico models predicted therapeutic synergy of two i...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 29a374fb-5ee6-591a-be3b-d2b12a2befdd
DOI: 10.1101/2025.04.29.651188

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

A structure-based modelling approach identifies effective drug combinations for RAS-mutant acute myeloid leukemiaDOI 10.1101/2025.04.29.651188Read

Dissecting RAF Inhibitor Resistance by Structure-based Modeling Reveals Ways to Overcome Oncogenic RAS Signaling.Semantic proximity Read

Small-molecule RAS/RAF Binding Inhibitors Allosterically Disrupt RAF Conformation and Exert Efficacy Against a Broad Spectrum of RAS-driven CancersSemantic proximity Read

Pan-RAF inhibitor exarafenib targets BRAF class II/III NSCLC and reveals ARAF-KSR1 resistance and combination strategies.Semantic proximity Read

Targeting the EGFR/RAS/RAF signaling pathway in anticancer research: a recent update on inhibitor design and clinical trials (2020-2023).Semantic proximity Read

Targeting BRAF Class II and III Mutations in NSCLC with the pan-RAF inhibitor Exarafenib Reveals ARAF-KSR1-Mediated Resistance and Rational Combination StrategiesSemantic proximity Read

Discovery of a highly potent pan-RAF inhibitor IHMT-RAF-128 for cancer treatment.Semantic proximity Read

Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia.Semantic proximity Read

The Discovery of Exarafenib (KIN-2787): Overcoming the Challenges of Pan-RAF Kinase Inhibition.Semantic proximity Read

Discovery of a highly potent pan-RAF inhibitor IHMT-RAF-128 for cancer treatmentSemantic proximity Read

Dual RAF inhibition outperforms RAF-MEK combinations for suppressing ERK signaling in KRAS mutant cells.Semantic proximity Read

TP-0903 is active in models of drug-resistant acute myeloid leukemia.Semantic proximity Read

Sphingosine-1-phosphate receptor modulators resensitize FLT3-ITD acute myeloid leukemia cells with <i>NRAS</i> mutations to FLT3 inhibitorsSemantic proximity Read