Eltanexor (KPT-8602) is an orally active exportin-1 (XPO1) inhibitor (EC50 = 60.9nM) [1]. By inhibiting the nuclear export protein XPO1, Eltanexor leads to the nuclear accumulation of tumor suppressor proteins, restoring their tumor suppressor function and selectively inducing apoptosis in cancer cells [2-3]. Eltanexor is primarily used to treat multiple myeloma and acute leukemia [4].
In U87 cells, decreased cell viability after Eltanexor (1nM-10μM; 5d) treatment [5]. In HCT116 cells, Eltanexor (1nM-10μM; 72h) treatment reduces cancer cell viability cells [6].
In acute myeloid leukemia PDX2 mice model, Eltanexor (10mg/kg; ig; 4 weeks) treatment significantly reduced bioluminescence and prolonged survival of mice [7]. In recurrent clival chordoma mice model, Eltanexor (10mg/kg; po; 6 weeks) treatment significantly reduced tumor volume [8].
References:
[1]. Cornell R F, Rossi A C, Baz R, et al. Eltanexor (KPT-8602), a second-generation selective inhibitor of nuclear export (SINE) compound, in patients with refractory multiple myeloma[J]. Blood, 2017, 130: 3134.
[2]. Lai C, Xu L, Dai S. The nuclear export protein exportin‐1 in solid malignant tumours: From biology to clinical trials[J]. Clinical and Translational Medicine, 2024, 14(5): e1684.
[3]. Azizian N G, Li Y. XPO1-dependent nuclear export as a target for cancer therapy[J]. Journal of hematology & oncology, 2020, 13(1): 61.
[4]. Richard S, Jagannath S. Targeting nuclear export proteins in multiple myeloma therapy[J]. BioDrugs, 2022, 36(1): 13-25.
[5]. Otte K, Zhao K, Braun M, et al. Eltanexor Effectively Reduces Viability of Glioblastoma and Glioblastoma Stem-Like Cells at Nano-Molar Concentrations and Sensitizes to Radiotherapy and Temozolomide[J]. Biomedicines, 2022, 10(9): 2145.
[6]. Evans A E, Afroz S, Magstadt A, et al. The XPO1 inhibitor Eltanexor modulates the Wnt/β-catenin signaling pathway to reduce colorectal cancer tumorigenesis[J]. Cancer Research Communications, 2025.
[7]. Prolonged X P O. Prolonged XPO1 inhibition is essential for optimal antileukemic activity in NPM1-mutated AML[J]. 2022.
[8]. Walker C J, Chang H, Henegar L, et al. Selinexor inhibits growth of patient derived chordomas in vivo as a single agent and in combination with abemaciclib through diverse mechanisms[J]. Frontiers in Oncology, 2022, 12: 808021.
Eltanexor (KPT-8602)是一种口服有效的输出蛋白-1（XPO1）抑制剂（EC50 = 60.9nM） [1]。通过抑制核输出蛋白XPO1，Eltanexor导致肿瘤抑制蛋白在核内聚集，恢复其肿瘤抑制功能，并选择性诱导癌细胞凋亡 [2-3]。Eltanexor主要用于治疗多发性骨髓瘤和急性白血病 [4]。
在U87细胞中，Eltanexor（1nM-10μM；5d）治疗后细胞活力降低 [5]。在HCT116细胞中，Eltanexor（1nM-10μM；72h）治疗可降低癌细胞活力 [6]。
在急性髓性白血病PDX2小鼠模型中，Eltanexor（10mg/kg；ig；4周）治疗显著降低了小鼠的生物发光并延长了小鼠的生存期 [7]。在复发性斜坡脊索瘤小鼠模型中，Eltanexor（10mg/kg；po；6周）治疗显著缩小了肿瘤体积 [8]。