Anticancer Effects of the Novel Pyrazolyl-Urea GeGe-3

• Published in: International journal of molecular sciences Vol. 25; no. 10; p. 5380
• Main Authors: Williams, Ashleigh, Cooper, Emma, Clark, Bethany, Perry, Laura, Ponassi, Marco, Iervasi, Erika, Brullo, Chiara, Greenhough, Alexander, Ladomery, Michael
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-05-2024
• Subjects: Angiogenesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Breast cancer; Cancer; Care and treatment; Cell adhesion & migration; Cell growth; Cell Line, Tumor; cell migration; Cell Movement - drug effects; cell proliferation; Cell Proliferation - drug effects; Crizotinib; Humans; Investigations; Kinases; Localization; Lung cancer; Metabolism; Nonsteroidal anti-inflammatory drugs; novel anticancer drugs; Physiological aspects; Prostate cancer; Protein binding; Proteins; pyrazole; Pyrazoles - chemistry; Pyrazoles - pharmacology; Urea; Urea - analogs & derivatives; Urea - chemistry; Urea - pharmacology; cell migration; pyrazole; novel anticancer drugs; cell proliferation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25105380

In a screen of over 200 novel pyrazole compounds, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl)ureido)-1
-pyrazole-4-carboxylate (named GeGe-3) has emerged as a potential anticancer compound. GeGe-3 displays potent anti-angiogenic properties through the presumptive targeting of the protein kinase DMPK1 and the Ca2
-binding protein calreticulin. We further explored the anticancer potential of GeGe-3 on a range of established cancer cell lines, including PC3 (prostate adenocarcinoma), SKMEL-28 (cutaneous melanoma), SKOV-3 (ovarian adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MDA-MB231, SKBR3, MCF7 (breast adenocarcinoma), A549 (lung carcinoma), and HeLa (cervix epithelioid carcinoma). At concentrations in the range of 10 μM, GeGe-3 significantly restricted cell proliferation and metabolism. GeGe-3 also reduced PC3 cell migration in a standard wound closure and trans-well assay. Together, these results confirm the anticancer potential of GeGe-3 and underline the need for more detailed pre-clinical investigations into its molecular targets and mechanisms of action.