Development, synthesis and validation of improved c‐Myc/Max inhibitors

• Published in: Journal of cellular and molecular medicine Vol. 28; no. 8; pp. e18272 - n/a
• Main Authors: Yıldırım, Sümbül, Kocabaş, Fatih, Mermer, Arif
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2024; John Wiley and Sons Inc
• Subjects: Adenocarcinoma; anti‐cancer; Breast cancer; Breast carcinoma; c-Myc protein; Cancer therapies; Cell cycle; Cell growth; Cell Line; Cell Nucleus; Cell Survival; Cell viability; Chemotherapy; c‐Myc; Ethanol; Fourier transforms; Humans; Lung cancer; Lung carcinoma; Male; Max; Myc protein; Original; Pancreatic cancer; Pancreatic carcinoma; Pancreatic Neoplasms; Prostate cancer; Prostate carcinoma; Proteins; Radiation; rhodanine; Tumor cell lines; Tumorigenesis; Tumors; ultrasonication; anti‐cancer; ultrasonication; Max; c‐Myc; rhodanine
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.18272

The pathophysiological foundations of various diseases are often subject to alteration through the utilization of small compounds, rendering them invaluable tools for the exploration and advancement of novel therapeutic strategies. Within the scope of this study, we meticulously curated a diverse library of novel small compounds meticulously designed to specifically target the c‐Myc/Max complex. We conducted in vitro examinations of novel c‐Myc inhibitors across a spectrum of cancer cell lines, including PANC1 (pancreatic adenocarcinoma), MCF7 (breast carcinoma), DU‐145 (prostate carcinoma), and A549 (lung cancer). The initial analysis involved a 25 μM dose, which enabled the identification of potent anticancer compounds effective against a variety of tumour types. We identified c‐Myc inhibitors with remarkable potency, featuring IC50 values as low as 1.6 μM and up to 40 times more effective than the reference molecule in diminishing cancer cell viability. Notably, c‐Myc‐i7 exhibited exceptional selectivity, displaying 37‐fold and 59‐fold preference for targeting prostate and breast cancers, respectively, over healthy cells. Additionally, we constructed drug‐likeness models. This study underscores the potential for in vitro investigations of various tumour types using novel c‐Myc inhibitors to yield ground‐breaking and efficacious anticancer compounds.