ABT-751 hydrochloride  (Synonyms: E7010 hydrochloride)

ABT-751 (E7010) hydrochloride is a novel, highly orally bioavailable sulfonamides antimitotic compound and tubulin binder. It prevents tubulin aggregation by binding to the colchicine site on β-tubulin, leading to cell cycle arrest in G2/M phase and inducing apoptosis, thus effectively preventing cell division. ABT-751 (E7010) hydrochloride induces autophagy by inhibiting the AKT/MTOR signaling pathway. ABT-751 (E7010) hydrochloride showed significant inhibition against various types of cancer cells, including lung, gastric, colon, and breast cancer^{[1][2][3][4][5][6][7][8][9]}.

ABT-751 hydrochloride (2 μM; 4, 8 , 24h) 在肝细胞癌衍生的 Hep-3B 细胞中具有破坏有丝分裂，破坏线粒体膜电位，诱导 ROS 生成和 DNA 损伤的作用^[6]。
ABT-751 hydrochloride (2 μM; 4, 8 , 24h) 在 Hep-3B 细胞中能造成 DNA 损伤，抑制细胞增殖和诱导 G2/M 细胞周期阻滞^[6]。
ABT-751 hydrochloride (2 μM; 4, 8 , 24h) 通过抑制 AKT/MTOR 信号通路来诱导 TP53 缺失的 Hep-3B 细胞自噬，以及通过 caspase 依赖性、外源性和内源性途径诱导凋亡。当外源性表达 TP53 基因时，会进一步增加 ABT-751 诱导的这些细胞的自噬和凋亡^[6]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

ABT-751 hydrochloride (100 mg/kg/day, 口服, 5 days on, 5 days off x2, 21天) 在神经母细胞瘤模型中具有明显的抑制效果，在横纹肌肉瘤和肾母细胞瘤模型中，可以引发肿瘤体积的显著减小或消退。ABT-751 对 Vincristine 与 Paclitaxel (HY-B0015) 有协同作用^[7]。
ABT-751 hydrochloride (100 mg/kg/day, 口服, 5 days on, 5 days off x2) 在小鼠前列腺、非小细胞肺癌和乳腺肿瘤异种移植模型中都对 Docetaxel (HY-B0011) 具有协同作用，提高对肿瘤的抑制作用^[8]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

407.87

C₁₈H₁₈ClN₃O₄S

141450-48-8

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Huang SM et al.,Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling., Nature. 2009 Oct 1;461(7264):614-20.  [Content Brief]

  [2]. Elizabeth Fox et al. A Phase I Study of ABT-751, an Orally Bioavailable Tubulin Inhibitor, Administered Daily for 21 Days Every 28 Days in Pediatric Patients with Solid Tumors Clin Cancer Res February 15, 2008 14; 1111

  [3]. Aggarwal C, et al. Antiangiogenic agents in the management of non-small cell lung cancer: where do we stand now and where are we headed?,Cancer Biol Ther. 2012 Mar;13(5):247-63.  [Content Brief]

  [4]. Silver M, Rusk A, Phillips B, Beck E, Jankowski M, Philibert J, Hahn K, Hershey E, McKeegan E, Bauch J, Krivoshik A, Khanna C.,Evaluation of the oral antimitotic agent (ABT-751) in dogs with lymphoma.,J Vet Intern Med. 2012 Mar-Apr;26(2):349-54. doi: 10.1111/j.1939-1676.2012.00892.x. Epub 2012 Feb 28.  [Content Brief]

  [5]. Gaynon PS, Harned TM; for the Therapeutic Advances in Childhood LeukemiaLymphoma (TACL) Consortium.  [Content Brief]

  [6]. Yoshimatsu K, et al. Mechanism of action of E7010, an orally active sulfonamide antitumor agent: inhibition of mitosis by binding to the colchicine site of tubulin. Cancer Res. 1997;57(15):3208-3213.  [Content Brief]

  [7]. Morton CL, et al. Evaluation of ABT-751 against childhood cancer models in vivo. Invest New Drugs. 2007;25(4):285-295.  [Content Brief]

  [8]. David Frost, et al. ABT-751, an oral antimitotic, shows additive and synergistic activity with docetaxel in preclinical models. Cancer Res 1 May 2007; 67 (9_Supplement): 1426.