(Z,E)-5-(4-Ethylbenzylidine)-2-thioxothiazolidin-4-one

10058-F4 (403811-55-2) effectively disables c-Myc by inhibiting the c-Myc-Max association and function.It prevents the growth of fibroblasts in a c-Myc-dependent manner. Downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells.10058-F4 induces cell cycle arrest, apoptosis and myeloid differentiation in human acute myeloid leukemia.Inhibits the MYCN/Max interaction leading to cell cycle arrest, apoptosis and neuronal differentiation in MYCN-amplified neuroblastoma cells.

A c-Myc inhibitor that induces apoptosis

ChEBI: 10058-F4 is a member of the class of thiazolidinones that is 2-sulfanylidene-1,3-thiazolidin-4-one which is substituted at position 5 by a (4-ethylphenyl)methylidene group. It is a cell permeable inhibitor of c-Myc-Max dimerization and exhibits antitumour effects in vivo. It downregulates c-Myc expression and upregulates CDK inhibitors, p21 and p27 resulting in the inhibition of proliferation, induction of apoptosis and cell cycle arrest in G0/G1 phase. It has a role as an apoptosis inducer and an antineoplastic agent. It is a thiazolidinone and an olefinic compound.

10058-F4 is a c-Myc inhibitor that induces cell-cycle arrest and apoptosis. 10058-F4 is a cell-permeable thiazolidinone that specificallly inhibits the c-Myc-Max interaction and prevents transactivation of c-Myc target gene expression. 10058-F4 inhibits tumor cell growth in a c-Myc-dependent manner both in vitro and in vivo (64 μM using c-Myc transfected Rat1a fibroblasts).

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The small-molecule 10058-F4 inhibits c-Myc, a transcriptional regulator involved in cell proliferation, differentiation, and apoptosis. Dysregulation of the oncoprotein c-Myc is common in human cancers. 10058-F4 inhibits transactivation of gene expression by c-Myc-Max heterodimers by disrupting the association between c-Myc and the transcription factor Max. 10058-F4 treatment of acute myeloid leukemia cells inhibited c-Myc expression and induced apoptosis and cell arrest at G0/G1. In a mouse neuroblastoma model, 10058-F4 inhibited transactivation by N-Myc-Max, resulting in cell cycle arrest, apoptosis, and tumor growth reduction. Ovarian cancer cells treated with 10058-F4 displayed reduced cell proliferation and enhanced effects of chemotherapeutic drugs. The 10058-F4 inhibitor likely upregulates FOXO transcription factors and downstream genes involved in ovarian G1 cell cycle arrest, apoptosis, and autophagic cell death. 10058-F4 promoted increased expression of thioredoxin-interacting protein in triple-negative breast cancer drug-resistant cells, which promoted reactive oxygen species synthesis and reversed doxorubicin-induced chemotherapy resistance.

[1] XIAOYING YIN. Low molecular weight inhibitors of Myc–Max interaction and function[J]. Oncogene, 2003, 22 40: 6151-6159. DOI:10.1038/sj.onc.1206641
[2] CHE-PIN LIN. Small-molecule c-Myc inhibitor, 10058-F4, inhibits proliferation, downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells.[J]. Anti-Cancer Drugs, 2007, 18 2: 161-170. DOI:10.1097/cad.0b013e3280109424
[3] MING-JER HUANG . A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia[J]. Experimental hematology, 2006, 34 11: Pages 1480-1489. DOI:10.1016/j.exphem.2006.06.019
[4] HANNA ZIRATH. MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2013: 10258-10263. DOI:10.1073/pnas.1222404110