WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406757
CAS#: 403811-55-2
Description: 10058-F4 is a potent and selective c-Myc inhibitor, which markedly increases valproic acid-induced cell death in Jurkat and CCRF-CEM T-lymphoblastic leukemia cells. 10058-F4 inhibits proliferation, downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells. 10058-F4 induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia.
MedKoo Cat#: 406757
Name: 10058-F4
CAS#: 403811-55-2
Chemical Formula: C12H11NOS2
Exact Mass: 249.0282
Molecular Weight: 249.346
Elemental Analysis: C, 57.80; H, 4.45; N, 5.62; O, 6.42; S, 25.72
Synonym: 10058-F4; 10058F4; 10058 F4.
IUPAC/Chemical Name: 5-[(4-ethylphenyl)methylene]-2-thioxo-4-thiazolidinone
InChi Key: SVXDHPADAXBMFB-JXMROGBWSA-N
InChi Code: InChI=1S/C12H11NOS2/c1-2-8-3-5-9(6-4-8)7-10-11(14)13-12(15)16-10/h3-7H,2H2,1H3,(H,13,14,15)/b10-7+
SMILES Code: O=C1NC(S/C1=C/C2=CC=C(CC)C=C2)=S
Appearance: Yellow solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | 10058-F4 is a c-Myc inhibitor that specificallly inhibits the c-Myc-Max interaction and prevents transactivation of c-Myc target gene expression. |
| In vitro activity: | 10058-F4 arrested AML cells at G0/G1 phase, downregulated c-Myc expression and upregulated CDK inhibitors, p21 and p27. Meanwhile, 10058-F4 induced apoptosis through activation of mitochondrial pathway shown by downregulation of Bcl-2, upregulation of Bax, release of cytoplasmic cytochrome C, and cleavage of caspase 3, 7, and 9. Furthermore, 10058-F4 also induced myeloid differentiation, possibly through activation of multiple transcription factors. Similarly, 10058-F4-induced apoptosis and differentiation could also be observed in primary AML cells. Reference: Exp Hematol. 2006 Nov;34(11):1480-9. https://linkinghub.elsevier.com/retrieve/pii/S0301-472X(06)00428-0 |
| In vivo activity: | Peak plasma 10058-F4 concentrations of approximately 300 μM are seen at 5 min and declined to below the detection limit at 360 min following a single iv dose. Plasma concentration versus time data are best approximated by a two-compartment, open, linear model. The highest tissue concentrations of 10058-F4 are found in fat, lung, liver, and kidney. Peak tumor concentrations of 10058-F4 are at least tenfold lower than peak plasma concentrations. Eight metabolites of 10058-F4 are identified in plasma, liver, and kidney. The terminal half-life of 10058-F4 is approximately 1 h, and the volume of distribution is >200 ml/kg. No significant inhibition of tumor growth is seen after i.v. treatment of mice with either 20 or 30 mg/kg 10058-F4. Reference: Cancer Chemother Pharmacol. 2009 Mar;63(4):615-25. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18509642/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 49.0 | 196.51 | |
| Ethanol | 11.0 | 44.11 |
The following data is based on the product molecular weight 249.346 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| In vitro protocol: | 1. Huang MJ, Cheng YC, Liu CR, Lin S, Liu HE. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Exp Hematol. 2006 Nov;34(11):1480-9. doi: 10.1016/j.exphem.2006.06.019. PMID: 17046567. 2. Lv M, Wang Y, Wu W, Yang S, Zhu H, Hu B, Chen Y, Shi C, Zhang Y, Mu Q, Ouyang G. C‑Myc inhibitor 10058‑F4 increases the efficacy of dexamethasone on acute lymphoblastic leukaemia cells. Mol Med Rep. 2018 Jul;18(1):421-428. doi: 10.3892/mmr.2018.8935. Epub 2018 Apr 27. PMID: 29749488. |
| In vivo protocol: | 1. 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. doi: 10.1007/s00280-008-0774-y. Epub 2008 May 29. PMID: 18509642; PMCID: PMC2752825. |
1: Jie Z, Jinna Z, Jingjun Z, Pengcheng L, Fang Y, Qinyang C, Taiyu C, Hequn J, Tao R. Antitumor Effects of 10058-F4 and Curcumin in Combination Therapy for Pancreatic Cancer In Vitro and In Vivo. J Healthc Eng. 2022 Mar 24;2022:1620802. doi: 10.1155/2022/1620802. PMID: 35368919; PMCID: PMC8970865.
2: Ghaffarnia R, Nasrollahzadeh A, Bashash D, Nasrollahzadeh N, Mousavi SA, Ghaffari SH. Inhibition of c-Myc using 10058-F4 induces anti-tumor effects in ovarian cancer cells via regulation of FOXO target genes. Eur J Pharmacol. 2021 Oct 5;908:174345. doi: 10.1016/j.ejphar.2021.174345. Epub 2021 Jul 13. PMID: 34270986.
3: Sayyadi M, Safaroghli-Azar A, Safa M, Abolghasemi H, Momeny M, Bashash D. NF- κB-dependent Mechanism of Action of c-Myc Inhibitor 10058-F4: Highlighting a Promising Effect of c-Myc Inhibition in Leukemia Cells, Irrespective of p53 Status. Iran J Pharm Res. 2020 Winter;19(1):153-165. doi: 10.22037/ijpr.2020.112926.14018. PMID: 32922477; PMCID: PMC7462502.
4: Sayyadi M, Safaroghli-Azar A, Pourbagheri-Sigaroodi A, Abolghasemi H, Anoushirvani AA, Bashash D. c-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis. Arch Med Res. 2020 Oct;51(7):636-644. doi: 10.1016/j.arcmed.2020.06.002. Epub 2020 Jun 14. PMID: 32553459.
5: Sheikh-Zeineddini N, Safaroghli-Azar A, Salari S, Bashash D. C-Myc inhibition sensitizes pre-B ALL cells to the anti-tumor effect of vincristine by altering apoptosis and autophagy: Proposing a probable mechanism of action for 10058-F4. Eur J Pharmacol. 2020 Mar 5;870:172821. doi: 10.1016/j.ejphar.2019.172821. Epub 2019 Nov 23. PMID: 31770526.
6: Sheikh-Zeineddini N, Bashash D, Safaroghli-Azar A, Riyahi N, Shabestari RM, Janzamin E, Safa M. Suppression of c-Myc using 10058-F4 exerts caspase-3-dependent apoptosis and intensifies the antileukemic effect of vincristine in pre-B acute lymphoblastic leukemia cells. J Cell Biochem. 2019 Aug;120(8):14004-14016. doi: 10.1002/jcb.28675. Epub 2019 Apr 7. PMID: 30957273.
7: Bashash D, Sayyadi M, Safaroghli-Azar A, Sheikh-Zeineddini N, Riyahi N, Momeny M. Small molecule inhibitor of c-Myc 10058-F4 inhibits proliferation and induces apoptosis in acute leukemia cells, irrespective of PTEN status. Int J Biochem Cell Biol. 2019 Mar;108:7-16. doi: 10.1016/j.biocel.2019.01.005. Epub 2019 Jan 9. PMID: 30639430.
8: Lv M, Wang Y, Wu W, Yang S, Zhu H, Hu B, Chen Y, Shi C, Zhang Y, Mu Q, Ouyang G. C‑Myc inhibitor 10058‑F4 increases the efficacy of dexamethasone on acute lymphoblastic leukaemia cells. Mol Med Rep. 2018 Jul;18(1):421-428. doi: 10.3892/mmr.2018.8935. Epub 2018 Apr 27. PMID: 29749488.
9: Zhang M, Fan HY, Li SC. Inhibition of c-Myc by 10058-F4 induces growth arrest and chemosensitivity in pancreatic ductal adenocarcinoma. Biomed Pharmacother. 2015 Jul;73:123-8. doi: 10.1016/j.biopha.2015.05.019. Epub 2015 Jun 1. PMID: 26211592.
10: Mu Q, Ma Q, Lu S, Zhang T, Yu M, Huang X, Chen J, Jin J. 10058-F4, a c-Myc inhibitor, markedly increases valproic acid-induced cell death in Jurkat and CCRF-CEM T-lymphoblastic leukemia cells. Oncol Lett. 2014 Sep;8(3):1355-1359. doi: 10.3892/ol.2014.2277. Epub 2014 Jun 24. PMID: 25120723; PMCID: PMC4114592.
11: 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. doi: 10.1007/s00280-008-0774-y. Epub 2008 May 29. PMID: 18509642; PMCID: PMC2752825.
12: Lin CP, Liu JD, Chow JM, Liu CR, Liu HE. Small-molecule c-Myc inhibitor, 10058-F4, inhibits proliferation, downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells. Anticancer Drugs. 2007 Feb;18(2):161-70. doi: 10.1097/CAD.0b013e3280109424. PMID: 17159602.
13: Huang MJ, Cheng YC, Liu CR, Lin S, Liu HE. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Exp Hematol. 2006 Nov;34(11):1480-9. doi: 10.1016/j.exphem.2006.06.019. PMID: 17046567.
