Abnormal activation of Mer kinase has been implicated in the oncogenesis of many human cancers including acute lymphoblastic and myeloid leukemia, non-small cell lung cancer, and glioblastoma. We have discovered a new family of small molecule Mer inhibitors, pyrazolopyrimidine sulfonamides, that potently inhibit the kinase activity of Mer. Importantly, these compounds do not demonstrate significant hERG activity in the PatchXpress assay. Through structure–activity relationship studies, 35 (UNC1062) was identified as a potent (IC₅₀ = 1.1 nM) and selective Mer inhibitor. When applied to live tumor cells, UNC1062 inhibited Mer phosphorylation and colony formation in soft agar. Given the potential of Mer as a therapeutic target, UNC1062 is a promising candidate for further drug development.

Mer 激酶的异常激活与许多人类癌症的发生有关，包括急性淋巴细胞白血病和骨髓性白血病、非小细胞肺癌和胶质母细胞瘤。我们发现了一个新的小分子 Mer 抑制剂家族，吡唑并嘧啶磺酰胺，可有效抑制 Mer 的激酶活性。重要的是，这些化合物在 PatchXpress 测定中并未表现出显着的 hERG 活性。通过结构-活性关系研究， 35 ( UNC1062 ) 被鉴定为有效的 (IC ₅₀ = 1.1 nM) 和选择性 Mer 抑制剂。当应用于活肿瘤细胞时， UNC1062抑制软琼脂中的 Mer 磷酸化和集落形成。鉴于 Mer 作为治疗靶点的潜力， UNC1062是进一步药物开发的有希望的候选者。