SJB3-019A is a novel and potent USP1 inhibitor, exhibiting an IC₅₀ value of 0.0781μM in K562 cells[1-2]. SJB-019A can be used in the study of leukemia and related diseases[3-4].
In vitro, MM.1S multiple myeloma cells were treated with SJB3-019A (0.1–1μM) for 24 hours. SJB3-019A significantly induced the activation of caspase-3/8/9 and the cleavage of PARP, inhibited the DNA repair pathway by increasing the ubiquitination levels of FANCD2/FANCI/PCNA, and simultaneously downregulated the expression of the ID protein family to promote cell differentiation[5]. B-cell acute lymphoblastic leukemia cells (CCRF-SB, Sup-B15, and KOPN-8) were treated with SJB3-019A (0.2–0.6μM) for 24 hours. SJB3-019A significantly induced G2/M phase arrest and apoptosis via the mitochondrial pathway, and reduced AKT phosphorylation levels by inhibiting the USP1-ID1 axis[6].
In vivo, nude mice and C57BL/6 mice bearing MHCC-97H cell xenografts or orthotopic liver tumors were administered daily intraperitoneal injections of SJB3-019A (0.5mg/kg) in combination with Doxorubicin (1mg/kg) for 2 weeks. SJB3-019A significantly enhanced the tumor suppression induced by Doxorubicin[7].
References:
[1] Tan L, Shan H, Han C, et al. Discovery of Potent OTUB1/USP8 Dual Inhibitors Targeting Proteostasis in Non-Small-Cell Lung Cancer. J Med Chem. 2022 Oct 27;65(20):13645-13659.
[2] Kong T, Laranjeira ABA, Letson CT, et al. RSK1 dependency in FLT3-ITD acute myeloid leukemia. Blood Cancer J. 2024 Nov 26;14(1):207.
[3] Ishikawa C, Mori N. Role of Ubiquitin-specific Protease 1 in the Pathogenesis and Treatment of Adult T-Cell Leukemia. Anticancer Res. 2025 Nov;45(11):4827-4840.
[4] Takahashi H, Yamanaka S, Kuwada S, et al. A Human DUB Protein Array for Clarification of Linkage Specificity of Polyubiquitin Chain and Application to Evaluation of Its Inhibitors. Biomedicines. 2020 Jun 4;8(6):152.
[5] Das DS, Das A, Ray A, et al. Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells. Clin Cancer Res. 2017 Aug 1;23(15):4280-4289.
[6] Kuang X, Xiong J, Lu T, et al. Inhibition of USP1 induces apoptosis via ID1/AKT pathway in B-cell acute lymphoblastic leukemia cells. Int J Med Sci. 2021 Jan 1;18(1):245-255.
[7] Lu Z, Zhang Z, Yang M, et al. Ubiquitin-specific protease 1 inhibition sensitizes hepatocellular carcinoma cells to doxorubicin by ubiquitinated proliferating cell nuclear antigen-mediated attenuation of stemness. Anticancer Drugs. 2022 Aug 1;33(7):622-631.
SJB3-019A是一种新颖的、有效的USP1抑制剂，对K562细胞USP1的IC₅₀为0.0781μM[1-2]。SJB3-019A可用于白血病等相关疾病的研究[3-4]。
在体外，SJB3-019A（0.1–1μM）处理多发性骨髓瘤细胞MM.1S 24小时，SJB3-019A显著诱导caspase-3/8/9激活和PARP裂解，并通过增加FANCD2/FANCI/PCNA泛素化水平抑制DNA修复通路，同时下调ID蛋白家族表达促进细胞分化[5]。SJB3-019A（0.2–0.6μM）处理B细胞急性淋巴细胞白血病细胞（CCRF-SB、Sup-B15和KOPN-8）24小时，SJB3-019A显著诱导G2/M期阻滞和线粒体途径凋亡，并通过抑制USP1-ID1轴降低AKT磷酸化水平[6]。
在体内，SJB3-019A（0.5mg/kg）联合Doxorubicin（1mg/kg）每日一次腹腔注射，用于处理MHCC-97H细胞异种移植瘤或原位肝肿瘤模型的裸鼠及C57BL/6小鼠2周。SJB3-019A显著增强了Doxorubicin诱导的肿瘤抑制[7]。