FLX925 / GSK - LARVOL DELTA

Ebf1 Is Involved in Primitive Myelopoiesis and Contributes in Leukemia Pathogenesis (ASH 2023) - "We treated EBF1-C534F, EBF1-WT, and control AML cell culture with CDK4 inhibitor: AMG925. We were surprised to find that the CDK4 inhibitor sufficiently suppressed the proliferation and reversed the prolonged S phase caused by EBF1 mutation. We investigated the myeloid-bias function of Ebf1 deficiency and the potential pathogenesis of EBF1 mutations of AML from the development view and were surprised to find CDK inhibitors as a potential drug for EBF1-deficient AML patients."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CEBPA • CORO • EBF1 • IL34 • IL6 • IRF8 • LYZ

High-throughput proteomic profiling reveals mechanisms of action of AMG925, a dual FLT3-CDK4/6 kinase inhibitor targeting AML and AML stem/progenitor cells. (PubMed, Ann Hematol) - "Mass cytometry identified pathways that may confer resistance to AMG925 in phenotypically defined AML stem/progenitor cells and demonstrated that combined blockade of FLT3-CDK4/6 and AKT/mTOR signaling facilitated stem cell death. Our findings provide a rationale for the mechanism-based inhibition of FLT3-CDK4/6 and for combinatorial approaches to improve the efficacy of FLT3 inhibition in both FLT3 wild-type and FLT3-mutated AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CDK4 • FLT3

FLT3 inhibitors in acute myeloid leukemia. (PubMed, J Hematol Oncol) - "In this review, we summarized the preclinical and clinical studies on new FLT3 inhibitors, including sorafenib, lestaurtinib, sunitinib, tandutinib, quizartinib, midostaurin, gilteritinib, crenolanib, cabozantinib, Sel24-B489, G-749, AMG 925, TTT-3002, and FF-10101. New generation FLT3 inhibitors and combination therapies may overcome resistance to first-generation agents."

Journal • Review