10058-F4 inhibits the growth of leukemic cells and dimerization of the c-Myc/Max heterodimerization to control the cell proliferation, apoptosis, and differentiation, and its aberrant expression. 10058-F4 increased FOXO1 mRNA in MedB-1 cells. 10058-F4 is most efficient in inducing neuronal differentiation and lipid accumulation in MYCN-amplified neuroblastoma cells. 10058-F4 could markedly suppresse the wild-type LKB1 loss-induced cell invasiveness. 10058-F4 increased the chemosensitivity of HepG2 cells to low-dose doxorubicin, 5-fluorouracil and cisplatin.
|Cell lines||PC-3 and DU145 cells|
|Preparation method||MTT assay
PC-3 cells (2 × 104 cells in logarithmic growth) were plated into 96-well culture plates and allowed to adhere to the plates for 24 h prior to the addition of 10058-F4 in medium containing 1% ethanol such that the final concentrations in the wells were 0.1-100 μM in medium containing 0.3% ethanol. After 72 h, 50 μl of 1 mg/ml MTT was added to each well. The cells were washed with medium and phosphate buffered saline, and 150 μl of DMSO was added to each well, followed by shaking for 5 min. The absorbance at 570 nm was read on DYNEX MRX Revelation microplate reader (Dynex, Vienna, VA, USA). Results were compared to wells containing cells treated with vehicle alone and were expressed as % inhibition. The IC50 was calculated using the Hill equation, the program ADAPT II, and data from three separate experiments.
|Incubation time||72 h|
|Animal models||SCID mice bearing DU145 or PC-3 xenografts|
|Formulation||cremophor EL:ethanol:saline (1:1:8 v/v/v) at a final concentration of 2 or 3 mg/ml|
|Dosages||20 or 30 mg/kg daily for 5 days for 2 weeks|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 40 mg/mL|
|Source||J Transl Med (2014). Figure 2.10058-F4|
|Cell Lines||HepG2 cells|
|Concentrations||100 or 130 μmol/l|
|Incubation Time||24 h|
|Results||10058-F4-induced growth inhibition is likely mediated by upregulation of p21 and indirect downregulation of cyclin D3.|
|Source||J Transl Med (2014). Figure 1.10058-F4|
|Cell Lines||HepG2 and Hep3B cells|
|Incubation Time||24 h|
|Results||In HepG2 cells treated with10058-F4, there were no detectable binding of c-Myc protein to the E-box-containing oligonucleotides|
Targeting of the MYCN Protein with Small Molecule c-MYC Inhibitors.
Müller I, et al. PloS one. 2014 May 23;9(5):e97285. PMID: 24859015.
The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss.
Tsai LH, et al. Oncogene. 2014 May 5. PMID: 24793789.
Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice.
Guo J, et al. Cancer Chemother Pharmacol. 2009 Mar;63(4):615-25. PMID: 18509642.
Small-molecule c-Myc inhibitor, 10058-F4, inhibits proliferation, downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells.
Lin CP, et al. Anticancer Drugs. 2007 Feb;18(2):161-170. PMID: 17159602.
A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia.
Huang MJ, et al. Experimental hematology. 2006 Nov;34(11):1480-9. PMID: 17046567.
|Related c-Myc Products|
10074-G5 is a c-Myc/Max interaction inhibitor, which binds to a different specific binding site (region) of C-Myc than 10054-F4.
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