新药的临床试验通常面临高达约45%的失败率，原因是安全性和毒性问题。重新运用具有良好安全记录的药物成为解决这一挑战的关键。结直肠癌是全球第三常见的癌症和第二常见的癌症相关死因。本研究侧重于RNA结合蛋白pumilio1（PUM1），这是PUF家族的一个成员，参与了转录后的基因表达调控。通过利用分子对接技术和FDA批准的药物，发现了针对PUM1的潜在抑制剂。值得注意的是，多拉塞特龙和可托那考根据概念密度泛函理论（Conceptual-DFT）计算结果显示出了强大的结合亲和力，疏水作用和有利的化学反应性。这两种化合物能有效减少细胞的存活率，IC50值分别为150 µM和175 µM，并在减少集落数量方面显示了长期的抑制效果。此外，它们对结肠癌干细胞也表现出抑制效果，表现为降低结肠球体的大小和数量。这些化合物诱导了凋亡，并在HCT116细胞中触发了执行凋亡酶3/7的激活，这可以通过凋亡酶3/7试验和AO/EB染色得到证实，而这些化合物的无毒效应则可以通过对非癌细胞系和溶血试验的存活率进行证实。此外，与对照组相比，治疗组的PUM1和癌症干细胞标志物的表达明显降低。总之，本研究突出了以PUM1为靶点的结直肠癌治疗的潜力。多拉塞特龙和可托那考根据抑制PUM1的方式显示出了作为有效的抗癌和抗癌干细胞药物的潜力，能够通过抑制PUM1诱导结肠癌细胞凋亡。

Clinical trials of new drugs often face a high failure rate of approximately 45 percent due to safety and toxicity concerns. Repurposing drugs with well-established safety profiles becomes crucial in addressing this challenge. Colon cancer ranks as the third most prevalent cancer and the second leading cause of cancer related mortality worldwide. This study focuses on the RNA-binding protein pumilio1 (PUM1), a member of the PUF family involved in post-transcriptional gene expression regulation. By utilizing molecular docking techniques and FDA-approved drugs, potential inhibitors against PUM1 were identified. Notably, dolasetron and ketoprofen demonstrated promising results, exhibiting strong binding affinity, hydrophobic interactions, and favorable chemical reactivity according to Conceptual-DFT calculations. Both compounds effectively reduced cell viability, with IC50 values of 150 µM and 175 µM, respectively and shows long term inhibitory effects as seen by reduced in number of colonies. Moreover, they exhibited inhibitory effects on colon cancer stem cells, as indicated by reduced colonospheroid size and numbers. Apoptosis is induced by these compounds and has triggered activation of executioner caspase 3/7 in HCT116 cells which is evident through a caspase 3/7 assay and AO/EB staining, while the non-toxic effect of these compounds was evident from viability against non-cancerous cell line and hemolysis assay. Additionally, the treatment group showed a significant decrease in PUM1 and cancer stem cell markers expression compared to the control group. In conclusion, this study highlights the potential of targeting PUM1 as a novel approach to colon cancer treatment. Dolasetron and ketoprofen demonstrate promise as effective anti-cancer and anti-cancer stem cell drugs, inducing apoptosis in colon cancer cells through inhibition of PUM1.