10058-F4
10058-F4 is a novel small-molecule inhibitor of c-Myc. 10058-F4 prevented the binding of c-Myc/Max dimers to its DNA targets, inhibited leukemic proliferation, and induced apoptosis through mitochondrial pathway, such as downregulation of Bcl-2, upregulation of Bax and release of cytoplasmic cytochrome C. [1]
10058-F4 blocks the C-MYC/Max heterodimerization which is required for c-Myc activity as a transcription factor. 10058-F4 efficiently inhibits the induction of PGC-1β mRNA by both HRG and IGF-1 and also abolishes the induction of PGC-1β protein levels by HRG and IGF-1, confirming that the induction of PGC-1b protein by these growth factors is a transcriptional event requiring C-MYC activity.[2] 10058-F4 acts not only to block c-Myc function through the mechanism of c-Myc/Max heterodimer dissociation, but it also resulted in decreased c-Myc mRNA levels (65%, n = 3) in lymphoma cells.[3]
References:
[1] Huang MJ, Cheng YC, Liu CR, Lin SF, Liu H. E. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Experimental Hematology. 2006; 34: 1480–1489.
[2] Ching-yi Chang, Dmitri Kazmin, Jeff S. Jasper, Rebecca Kunder, William J. Zuercher, Donald P. McDonnell. The Metabolic Regulator ERRα, a Downstream Target of HER2/IGF-1R, as a Therapeutic Target in Breast Cancer. Cancer Cell. 18 October 2011. 20(4): 500-510.
[3] Ilsa Gomez-Curet, R. Serene Perkins, Ryan Bennett, Katherine L. Feidler, Stephen P. Dunn, Leslie J. Krueger. c-Myc inhibition negatively impacts lymphoma growth. Journal of Pediatric Surgery. January 2006. 41(1): 207-211.
- 1. Na Sun, Jiawa Wang, et al. "Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4." Cell Death Dis 15, 861 (2024).
- 2. Josh L. Stern, Lindsay F. Rizzardi, et al."Apurinic/apyrimidinic endodeoxyribonuclease 2 (APEX2/APE2) is required for efficient expression of TERT in human embryonic stem cells." September 23, 2024.
- 3. Spandana Kotian, Lindsay F. Rizzardi, et al. "MEK1/2 kinases cooperate with c-Myc:MAX to prevent polycomb repression of TERT in human pluripotent stem cells." September 18, 2024.
- 4. Dongfang Tang, Tao Huang, et al. "MYC/NBS1-Mediated DNA Damage Response is Involved in the Inhibitory Effect of Hydroxysafflor Yellow A on Glioma Cells." Drug Des Devel Ther. 2021 Apr 28;15:1749-1763. PMID:33953544
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 249.35 |
| Cas No. | 403811-55-2 |
| Formula | C12H11NOS2 |
| Solubility | ≥24.9 mg/mL in DMSO; insoluble in H2O; ≥2.64 mg/mL in EtOH |
| Chemical Name | (5E)-5-[(4-ethylphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one |
| SDF | Download SDF |
| Canonical SMILES | CCC1=CC=C(C=C1)C=C2C(=O)NC(=S)S2 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
HL-60, U937 and NB-4 cells |
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Preparation method |
The solubility of this compound in DMSO is > 12.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0, 30, 60, 100 and 150 μM; 72 hrs |
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Applications |
All AML cell lines (HL-60, U937 and NB-4) were sensitive to 10058-F4 in a dose-dependent manner. At the dose of 100 μM, 10058-F4 significantly induced apoptosis of AML cell after the 72-hr treatment. In addition, 10058-F4 decreased levels of c-Myc proteins in all AML cell lines. |
| Animal experiment [2]: | |
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Animal models |
SCID mice bearing DU145 or PC-3 human prostate cancer xenografts |
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Dosage form |
20 or 30 mg/kg; i.v.; q.d., 5 days per week, for 2 weeks |
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Applications |
In mice bearing PC-3 xenografts, intravenous treatment with 20 or 30 mg/kg 10058-F4 resulted in the maximum mean %TC values of 72.3 and 72.9%, respectively. Similarly, in mice bearing DU145 xenografts, 30 mg/kg 10058-F4 resulted in a maximum mean %TC value of 85%. 10058-F4 showed lack of effect in both models. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Huang MJ, Cheng YC, Liu CR, Lin SF, Liu H. E. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Experimental Hematology. 2006; 34: 1480–1489. [2]. Guo J, Parise RA, Joseph E, Egorin MJ, Lazo JS, Prochownik EV, Eiseman JL. Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice. Cancer Chemother Pharmacol. 2009 Mar;63(4):615-25. | |
| Description | 10058-F4 is a small-molecule and cell-permeable inhibitor of c-Myc-Max dimerization. | |||||
| Targets | c-Myc-Max dimerization | |||||
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Quality Control & MSDS
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