EHop-016 is a potent inhibitor of Rac GTPase Rac1, with an IC50 value of 1.1μM[1]. EHop-016 targets the Rac protein and reduces the activity of the downstream effector molecule, p21-activated kinase (PAK), thereby demonstrating cytotoxicity[2]. EHop-016 has been widely used as an anti-cancer agent, inhibiting tumor growth in both cell models and mouse models[3].
In vitro, EHop-016 treatment for 48 hours significantly inhibited the proliferation of Calu1, A549, and HOP62 cells, with IC50 values of 4.3, 9.12, and 4.8μM, respectively[4]. EHop-016 reduced the number of viable MOLM-13 cells with an EC50 of 11.3µM after 48h incubation[5]. Treatment with 5μM EHop-016 for 1 hour can inhibit the glucose-induced actin remodeling in INS-1 832/13 cells[6].
In vivo, EHop-016 treatment via intraperitoneal injection at a dose of 25mg/kg (three times a week) for 8 weeks significantly reduced tumor growth without causing weight changes in GFP-MDA-MB-435 cell-xenograft mice[7]. Administering a 30mg/kg dose of EHop-016 by intraperitoneal injection three times a week for 55 days led to a reduction in macrophage infiltration in the tumors of breast cancer mouse models, and decreased the activation of myeloid cells[8].
References:
[1] Montalvo-Ortiz B L, Castillo-Pichardo L, Hernández E, et al. Characterization of EHop-016, novel small molecule inhibitor of Rac GTPase[J]. Journal of Biological Chemistry, 2012, 287(16): 13228-13238.
[2] Crespo G E V, Hernández E, Vlaar C, et al. The novel Rac inhibitor HV-107 as a potential therapeutic for metastatic breast cancer[J]. Cancer Research, 2018, 78(13_Supplement): 4185-4185.
[3] Asencio‐Torres G, Hernández E, Vlaar C, et al. Novel Rac Inhibitors as Targeted Therapeutics for Metastatic Breast Cancer[J]. The FASEB Journal, 2018, 32: 804.14-804.14.
[4] Yang J, Qiu Q, Qian X, et al. Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer[J]. Molecular cancer, 2019, 18(1): 171.
[5] Hemsing A L, Førde J L, Reikvam H, et al. The Rac1-inhibitor EHop-016 attenuates AML cell migration and enhances the efficacy of daunorubicin in MOLM-13 transplanted zebrafish larvae[J]. Translational Oncology, 2024, 40: 101876.
[6] Veluthakal R, Tunduguru R, Arora D K, et al. VAV2, a guanine nucleotide exchange factor for Rac1, regulates glucose-stimulated insulin secretion in pancreatic beta cells[J]. Diabetologia, 2015, 58(11): 2573-2581.
[7] Castillo-Pichardo L, Humphries-Bickley T, De La Parra C, et al. The Rac inhibitor EHop-016 inhibits mammary tumor growth and metastasis in a nude mouse model[J]. Translational oncology, 2014, 7(5): 546-555.
[8] Torres-Sanchez A, Rivera-Robles M, Castillo-Pichardo L, et al. Rac and Cdc42 inhibitors reduce macrophage function in breast cancer preclinical models[J]. Frontiers in Oncology, 2023, 13: 1152458.
EHop-016是一种高效的Rac GTP酶Rac1抑制剂，IC50值为1.1μM[1]。EHop-016通过靶向Rac蛋白并降低下游效应分子p21激活激酶的活性，进而发挥细胞毒性作用[2]。EHop-016已作为抗癌剂广泛应用于细胞模型和小鼠模型中抑制肿瘤生长[3]。
在体外，EHop-016处理48小时能显著抑制Calu1、A549和HOP62细胞的增殖，IC50值分别为4.3μM、9.12μM和4.8μM[4]。经EHop-016处理48小时后，MOLM-13活细胞数量减少，EC50值为11.3µM[5]。使用5μM的EHop-016处理INS-1 832/13细胞1小时，可抑制葡萄糖诱导的肌动蛋白重构[6]。
在体内，每周三次腹腔注射25mg/kg剂量的EHop-016连续8周，能显著抑制GFP-MDA-MB-435细胞移植瘤小鼠的肿瘤生长，且未引起体重变化[7]。每周三次腹腔注射30mg/kg剂量的EHop-016连续55天，可减少乳腺癌小鼠模型肿瘤中的巨噬细胞浸润，并降低髓系细胞的活化水平[8]。