Myeloid cell leukemia sequence 1 (MCL-1) is an antiapoptotic protein that plays a key role in promoting cell survival in multiple myeloma (MM), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL). Overexpression of MCL-1 is associated with treatment resistance and poor prognosis; thus, MCL-1 inhibitors are rational therapeutic options for malignancies depending on MCL-1. Several MCL-1 inhibitors have entered clinical trials, including AZD5991, S64315, AMG 176, and AMG 397. A key area of investigation is whether MCL-1 inhibitors will complement the activity of BCL-2 inhibitors, such as venetoclax, and synergistically enhance anti-tumor efficacy when given in combination with other anti-cancer drugs. Another important question is whether a safe therapeutic window can be found for this new class of inhibitors. In summary, inhibition of MCL-1 shows potential as a treatment for hematologic malignancies and clinical evaluation of MCL-1 inhibitors is currently underway.

髓细胞白血病序列 1 (MCL-1) 是一种抗凋亡蛋白，在促进多发性骨髓瘤 (MM)、急性髓性白血病 (AML) 和非霍奇金淋巴瘤 (NHL) 的细胞存活中起关键作用。MCL-1的过度表达与治疗抵抗和预后不良有关；因此，MCL-1 抑制剂是依赖于 MCL-1 的恶性肿瘤的合理治疗选择。多种 MCL-1 抑制剂已进入临床试验，包括 AZD5991、S64315、AMG 176 和 AMG 397。研究的一个关键领域是 MCL-1 抑制剂是否会补充 BCL-2 抑制剂（如 venetoclax）的活性，并协同增强与其他抗癌药物联合使用时具有抗肿瘤功效。另一个重要问题是是否可以为这类新型抑制剂找到安全的治疗窗口。总之，MCL-1 的抑制显示出治疗血液系统恶性肿瘤的潜力，目前正在进行 MCL-1 抑制剂的临床评估。