Supplementary Tables 1 - 6, Figures 1 - 7 from Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 “Gatekeeper” F691L Mutation with PLX3397

作者：Catherine Choy Smith, Chao Zhang, Kimberly C. Lin, Elisabeth A. Lasater, Ying Zhang, Evan Massi, Lauren E. Damon, Matthew Pendleton, Ali Kashif Bashir, Robert Sebra, Alexander E. Perl, Andrew Kasarskis, Rafe Shellooe, Garson Tsang, Heidi Carias, Benjamin James Powell, Elizabeth A. Burton, Bernice Matusow, Jiazhong Zhang, Wayne R. Spevak, Prabha N. Ibrahim, Mai Hope Le, Henry H. Hsu, Gaston G. M. Habets, Brian L. West, Gideon E. Bollag, Neil P. Shah · 年份：2023 · DOI：10.1158/2159-8290.22531562.v1 · 研究领域：Chronic Lymphocytic Leukemia Research、Chronic Myeloid Leukemia Treatments

Supplementary Table 1. Crystallographic Data and Refinement statistics. Supplementary Table 2. Comparing Target Inhibition by Quizartinib and PLX3397 in Engineered Ba/F3 cells Expressing FLT3-ITD, FLT3-ITD/F691L and FLT3-ITD/D835Y. Supplementary Table 3. Inhibitory Concentration (IC50) for Proliferation of Human Leukemia Cell Lines in PLX3397. Supplementary Table 4. 48 Hour Inhibitory Concentration (IC50) for Proliferation of Ba/F3 Cells Expressing Quizartinib and PLX3397-Resistant FLT3-ITD Mutant Isoforms. Supplementary Table 5. Patient Characteristics. Supplementary Table 6. Low Frequency FLT3 Kinase Domain Mutations of Uncertain Significance Observed at the Time of Resistance in Patient 1.14. Supplementary Figure 1. Composite omit map contoured at 1sigma level for the bound quizartinib and a structural water molecule. Supplementary Figure 2. Comparing the actual and previously predicted binding modes of quizartinib. Supplementary Figure 3. Structural model showing that D835 induces the DFG-in conformation of the activation loop, resulting in an orientation of F830 that precludes quizartinib binding. Supplementary Figure 4. Structural superposition of quizartinib (green) and PLX3397 (orange) highlighting the key structural difference responsible for their different susceptibilities to L691. Supplementary Figure 5. PLX3397 Inhibits FLT3 Signaling In Vitro. Supplementary Figure 6. Molm14 F691L Cells Demonstrate Resistance to Quizartinib. Supplementary Figure 7. Activity of PL...