Identification of GNF-7 as an inhibitor of leukemia cells with mutant RAS. Using Ba/F3-NRAS-G12D cells, a chemical screen was performed in the presence or absence of IL-3. A unique and diverse library of 450 multitargeted kinase inhibitors was screened. (A) Relative growth of Ba/F3-NRAS-G12D cells in the screen was cultured in the absence of IL-3 vs the presence of IL-3. GNF-6 was identified as a hit in the screen. (B) IC₅₀s of GNF-6 and its analogs tested against Ba/F3-NRAS-G12D cells in the absence of IL-3 vs the presence of IL-3. (C) IC₅₀ of GNF-7 tested against a panel of human leukemia cell lines expressing WT or mutated NRAS gene. Cell lines expressing mutated FLT-3 were excluded. (D) A comparison was made of IC₅₀ for GNF-7 as it was tested against human leukemia cell lines with or without NRAS mutation. Data are represented as mean ± standard error of the mean. (E) Enrichment plot of a gene set NRAS EXTINCTION DOWN (as described in “Results”) and its size, NES (normalized enrichment score), and FDR (false discovery rate) q-value for OCI-AML3 cells and KO52 cells. (F) IC₅₀ of GNF-7 was tested against Ba/F3-TYK2 E957D, Ba/F3-c-KIT insAY, and Ba/F3-NRAS-G12D cells. wt, wild type. **P < .01.