AP-III-a4 hydrochloride is the first non-substrate analog inhibitor of enolase (IC50 = 0.576μM) [1]. AP-III-a4 hydrochloride induces cell death under hypoxia and inhibits cancer cell migration and invasion by downregulating AKT and Bcl-xL expression [1]. AP-III-a4 hydrochloride is often used in cancer research [2-3].
In HCT116 cells, AP-III-a4 hydrochloride (10μM, 24h) induced cell death under hypoxia and inhibited cancer cell migration and invasion by downregulating AKT and Bcl-xL expressions [1]. In NCI-H929 cells, AP-III-a4 hydrochloride (0.2-1.6μM; 72h) inhibits the proliferation of cancer cells [4]. In H9c2 cells, AP-III-a4 hydrochloride (10μM, 24h) inhibitor group displayed markedly reduced glucose and lactate levels [5].
In the Multiple myeloma (MM) xenograft model, the combination of AP-III-a4 hydrochloride (10mg/kg; ip; 15d) and BTZ has a more significant growth inhibitory effect in vivo than AP-III-a4 hydrochloride or BTZ alone [4].
References:
[1]. Jung DW, Kim WH, Park SH, et al. A unique small molecule inhibitor of enolase clarifies its role in fundamental biological processes. ACS chemical biology. 2013 Jun 21; 8(6): 1271-1282.
[2]. Chen X, Xu H, Wu N, et al. Interaction between granulin A and enolase 1 attenuates the migration and invasion of human hepatoma cells. Oncotarget. 2017 Mar 17; 8(18): 30305.
[3]. Wang C, Huang M, Lin Y, et al. ENO2-derived phosphoenolpyruvate functions as an endogenous inhibitor of HDAC1 and confers resistance to antiangiogenic therapy. Nature Metabolism. 2023 Oct; 5(10): 1765-1786.
[4]. Gao X, Feng Q, Zhang Q, et al. Targeting enolase 1 reverses bortezomib resistance in multiple myeloma through YWHAZ/Parkin axis. Journal of Biomedical Science. 2025 Jan 20; 32(1): 9.
[5]. Guo Z, Liu S, Hou X, et al. Isorhamnetin Attenuates Isoproterenol-Induced Myocardial Injury by Reducing ENO1 (Alpha-Enolase) in Cardiomyocytes. Antioxidants. 2025 May 11; 14(5): 579.
AP-III-a4 hydrochloride是第一个非底物类似物烯醇化酶抑制剂（IC50 = 0.576μM） [1]。AP-III-a4 hydrochloride在缺氧条件下诱导细胞死亡，并通过下调AKT和Bcl-xL的表达来抑制癌细胞的迁移和侵袭 [1]。AP-III-a4盐酸盐常用于癌症研究 [2-3]。
在HCT116细胞中，AP-III-a4 hydrochloride（10μM，24h）在缺氧条件下诱导细胞死亡，并通过下调AKT和Bcl-xL的表达来抑制癌细胞的迁移和侵袭 [1]。在NCI-H929细胞中，AP-III-a4 hydrochloride（0.2-1.6μM；72h）抑制癌细胞的增殖 [4]。在H9c2细胞中，AP-III-a4 hydrochloride（10μM，24h）抑制剂组显著降低葡萄糖和乳酸水平 [5]。
在多发性骨髓瘤（MM）异种移植模型中，AP-III-a4 hydrochloride（10mg/kg；ip；15d）与BTZ联合用药比单独使用AP-III-a4盐酸盐或BTZ具有更显著的体内生长抑制作用 [4]。