EOAI3402143 is a novel, multi-target deubiquitinase inhibitor. EOAI3402143 promotes tumor cell apoptosis by inhibiting the activity of USP9x, USP24, and USP5 in a dose-dependent manner[1-2]. EOAI3402143 can be used in research related to melanoma, multiple myeloma, and pancreatic cancer[3-4].
In vitro, EOAI3402143 (2–8µM) was used to treat non-small cell lung cancer cells for 24–72 hours. EOAI3402143 significantly inhibited the proliferation and viability of the cancer cells and downregulated the expression level of cyclin D1 in the cells[5]. EOAI3402143 (2–8µM) was also used to treat JAK2-V617F-positive leukemia cells for 24–72 hours. EOAI3402143 markedly inhibited the proliferation and induced apoptosis of JAK2-V617F-dependent cells, while downregulating the activity of the autophosphorylated JAK2-V617F pathway[6].
In vivo, EOAI3402143 (2.5–15mg/kg) was administered via intraperitoneal injection once daily to mice bearing MM1.S myeloma xenografts for 2–4 weeks. EOAI3402143 significantly inhibited tumor growth, induced tumor regression, and downregulated the activity of Usp9x/Usp24 and the protein expression level of Mcl-1 in the tumor tissues[7]. EOAI3402143 (5mg/kg or 10mg/kg) was injected intraperitoneally every other day for 28 days into BALB/c nude mice bearing H1299 cell xenografts. EOAI3402143 significantly inhibited tumor growth and showed no significant toxic effects on the mice's body weight, pathological status of major organs, or serum biochemical indices[8].
References:
[1] Potu H, Peterson LF, Pal A, et al. Usp5 links suppression of p53 and FAS levels in melanoma to the BRAF pathway. Oncotarget. 2014 Jul 30;5(14):5559-69.
[2] Chen W, Shan Y, Wang M, et al. Chicoric acid exerts therapeutic effects in DSS-induced ulcerative colitis by targeting the USP9X/IGF2BP2 axis. Br J Pharmacol. 2025 Oct;182(20):4968-4983.
[3] Wang J, Fang S, Jiang Y, et al. Unraveling the Mechanism of Action of Ubiquitin-Specific Protease 5 and Its Inhibitors in Tumors. Clin Med Insights Oncol. 2024 Oct 9;18:11795549241281932.
[4] Akiyama H, Umezawa Y, Ishida S, et al. Inhibition of USP9X induces apoptosis in FLT3-ITD-positive AML cells cooperatively by inhibiting the mutant kinase through aggresomal translocation and inducing oxidative stress. Cancer Lett. 2019 Jul 1;453:84-94.
[5] Zhang Z, Cui Z, Xie Z, et al. Deubiquitinase USP5 promotes non-small cell lung cancer cell proliferation by stabilizing cyclin D1. Transl Lung Cancer Res. 2021 Oct;10(10):3995-4011.
[6] Akiyama H, Umezawa Y, Watanabe D, et al. Inhibition of USP9X Downregulates JAK2-V617F and Induces Apoptosis Synergistically with BH3 Mimetics Preferentially in Ruxolitinib-Persistent JAK2-V617F-Positive Leukemic Cells. Cancers (Basel). 2020 Feb 10;12(2):406.
[7] Peterson LF, Sun H, Liu Y, et al. Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies. Blood. 2015 Jun 4;125(23):3588-97.
[8] Xu J, Liu W, Chen L, et al. EOAI3402143 inhibits lung adenocarcinoma progression through the NF-κB/NR4A1 pathway. Acta Biochim Biophys Sin (Shanghai). 2025 Oct 9.
EOAI3402143是一种新型的、多靶点的去泛素化酶抑制剂。EOAI3402143可剂量依赖性地抑制USP9x、USP24和USP5的活性来促进肿瘤细胞凋亡[1-2]。EOAI3402143可用于黑色素瘤、多发性骨髓瘤和胰腺癌的相关研究[3-4]。
在体外，EOAI3402143（2–8μM）处理非小细胞肺癌细胞24–72小时。EOAI3402143可显著抑制非小细胞肺癌细胞的增殖与活力，同时下调细胞中周期蛋白D1的表达水平[5]。EOAI3402143（2–8μM）处理JAK2-V617F阳性的白血病细胞24–72小时。EOAI3402143显著地抑制JAK2-V617F依赖细胞的增殖并诱导其凋亡，同时下调自磷酸化的JAK2-V617F通路活性[6]。
在体内，EOAI3402143（2.5–15mg/kg）每日一次腹腔注射于携带MM1.S骨髓瘤异种移植瘤的小鼠，持续2–4周。EOAI3402143显著抑制了肿瘤生长并诱导了肿瘤消退，同时下调了肿瘤组织中Usp9x/Usp24的活性和Mcl-1的蛋白表达水平[7]。EOAI3402143（5mg/kg或10mg/kg）每两天一次腹腔注射于携带H1299细胞异种移植瘤的BALB/c裸鼠28天。EOAI3402143显著抑制了肿瘤的生长，同时对小鼠的体重、主要器官病理状态及血清生化指标未产生显著毒性影响[8]。