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Tumor recurrence from cancer stem cells (CSCs) and metastasis often occur post-treatment in colorectal cancer (CRC), leading to chemoresistance and resistance to targeted therapy. <i>MYC</i> is a transcription factor in the nuclei that modulates cell growth and development, and regulates immune response in an antitumor direction by mediating programmed death ligand 1 (<i>PD-L1</i>) and promoting CRC tumor recurrence after adjuvant chemotherapy. However, the molecular mechanism through which <i>c-MYC</i> maintains stemness and confers treatment resistance still remains elusive in CRC. In addition, recent reports demonstrated that CRC solid colon tumors expresses C-X-C motif chemokine ligand 8 (<i>CXCL8</i>). Expression of <i>CXCL8</i> in CRC was reported to activate the expression of PD-L1 immune checkpoint through c-MYC, this ultimately induces chemoresistance in CRC. Accumulating studies have also demonstrated increased expression of <i>CXCL8</i>, matrix metalloproteinase 7 (<i>MMP7</i>), tissue inhibitor of metalloproteinase 1 (<i>TIMP1</i>), and epithelial-to-mesenchymal transition (<i>EMT</i>) components, in CRC tumors suggesting their potential collaboration to promote <i>EMT</i> and CSCs. <i>TIMP1</i> is <i>MMP</i>-independent and regulates cell development and apoptosis in various cancer cell types, including CRC. Recent studies showed that <i>TIMP1</i> cleaves <i>CXCL8</i> on its chemoattractant, thereby influencing its mechanistic response to therapy. This therefore suggests crosstalk among the <i>c-MYC</i>/<i>CXCL8</i>/<i>TIMP1</i> oncogenic signatures. In this study, we explored computer simulations through bioinformatics to identify and validate that the <i>MYC</i>/<i>CXCL8</i>/<i>TIMP1</i> oncogenic signatures are overexpressed in CRC, Moreover, our docking results exhibited putative binding affinities of the above-mentioned oncogenes, with our novel small molecule, RV59, Finally, we demonstrated the anticancer activities of RV59 against NCI human CRC cancer cell lines both as single-dose and dose-dependent treatments, and also demonstrated the <i>MYC</i>/<i>CXCL8</i>/<i>TIMP1</i> signaling pathway as a potential RV59 drug target.