Tyrosine kinase inhibitors have revolutionized the world of cancer treatment in recent years, profoundly improving survival of patients with chronic myeloid leukemia (CML) and beyond. However, off-target toxicities of these inhibitors are well-described, and resistance has become a paramount concern. Novel allosteric inhibitors of the Abelson (ABL) family of tyrosine kinases, including GNF-2, GNF-5, and ABL-001, are equipped to overcome these issues. Several contemporary studies have demonstrated their potential efficacy in three key areas: primary hematologic and solid malignancies, metastasis, and combination with other small molecules. Further, ongoing clinical trials are investigating the efficacy of ABL-001 for the treatment of CML and recurrent solid tumors. This work reviews the current literature of the preclinical testing of GNF-2 and GNF-5 and the preclinical and clinical testing of ABL-001. Future research will continue to evaluate these promising inhibitors as both first-line therapy for solid tumors and salvage therapy when more traditional drugs such as imatinib fail.

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ABL 激酶的变构抑制：癌症的治疗潜力

近年来，酪氨酸激酶抑制剂彻底改变了癌症治疗领域，极大地提高了慢性粒细胞白血病 (CML) 及其他患者的生存率。然而，这些抑制剂的脱靶毒性得到了很好的描述，耐药性已成为首要问题。Abelson (ABL) 酪氨酸激酶家族的新型变构抑制剂，包括 GNF-2、GNF-5 和 ABL-001，可以克服这些问题。几项当代研究已经证明了它们在三个关键领域的潜在功效：原发性血液学和实体恶性肿瘤、转移以及与其他小分子的组合。此外，正在进行的临床试验正在研究 ABL-001 治疗 CML 和复发性实体瘤的疗效。这项工作回顾了 GNF-2 和 GNF-5 的临床前试验以及 ABL-001 的临床前和临床试验的当前文献。未来的研究将继续评估这些有前景的抑制剂作为实体瘤的一线治疗和更传统的药物（如伊马替尼）失败时的挽救治疗。