Figure 4 from Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR–ABL–Positive Leukemia

作者：Ziwei Luo, Chencen Lin, Chuwei Yu, Changxian Yuan, Wenyong Wu, Xiaowei Xu, Renhong Sun, Yan Jia, Yafang Wang, Jie Shen, Dingyan Wang, Sinan Wang, Hualiang Jiang, Biao Jiang, Xiaobao Yang, Chengying Xie · 年份：2025 · DOI：10.1158/0008-5472.28122535 · 研究领域：Chronic Myeloid Leukemia Treatments、Chronic Lymphocytic Leukemia Research、Acute Lymphoblastic Leukemia research

SIAIS562055 combined with KRAS inhibitors overcomes drug resistance. A, Western blot analysis of SOS1 in Ba/F3 cells transformed with or without KRAS mutation after treatment with SIAIS562055 (1,000 nmol/L) or BI-3406 (1,000 nmol/L) for 24 hours. B, Antiproliferative effects of SIAIS562055 on Ba/F3 cells transformed with or without KRAS mutations for 72 hours. Histogram shows the IC50 values of compounds in two-dimensional (2D) cultured cells. C, Cell proliferative inhibition of MIA PaCa-2 and MIA PaCa-2/R cells treated with AMG510 and MRTX849 for 72 hours. Histogram shows the IC50 values of compounds and resistance factors (RF) in 2D cultured cells. D, Western blot analysis of SOS1 by SIAIS562055 in MIA PaCa-2 and MIA PaCa-2/R cells for 72 hours. MIA PaCa-2/R xenograft-bearing mice received vehicle, SIAIS562055, and MRTX849, alone or in combination, then, the relative tumor volumes (E) and mouse body weights (F) were tested. qd, once a day. G, Western blot analysis of SOS1, pERK, and cleaved caspase-3 in MIA PaCa-2/R xenograft tumor tissues. Data about relative tumor volumes and body weights are presented as mean ± SEM, n = 5, whereas other statistical data are presented as mean ± SD, n = 3. **, P < 0.01; ***, P ...