WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 530576
CAS#: 413611-93-5
Description: 10074-G5 is a c-Myc/Max interaction inhibitor. 10074-G5, similarly to 10058-F4 (#F3680), specifically inhibits this interaction by binding to c-Myc, thus preventing C-Myc specific DNA binding and target genes regulation.
MedKoo Cat#: 530576
Name: 10074-G5
CAS#: 413611-93-5
Chemical Formula: C18H14N4O3
Exact Mass: 334.335
Molecular Weight: 334.335
Elemental Analysis: C, 64.67; H, 4.22; N, 16.76; O, 14.36
Synonym: 10074-G5; 10074G5; 10074 G5;
IUPAC/Chemical Name: N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine
InChi Key: KMJPYSQOCBYMCF-UHFFFAOYSA-N
InChi Code: InChI=1S/C18H12N4O3/c23-22(24)16-11-10-15(17-18(16)21-25-20-17)19-14-9-5-4-8-13(14)12-6-2-1-3-7-12/h1-11,19H
SMILES Code: O=[N+]([O-])C1=CC=C(C2=NON=C21)NC3=CC=CC=C3C4=CC=CC=C4
Appearance: 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
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: | 10074-G5 is an inhibitor of c-Myc-Max dimerization with an IC50 of 146 μM. |
| In vitro activity: | As shown in Fig. 2A, exposure of MDA-MB-231 cells with 10074-G5 at 10 μM, 25 μM and 50 μM decreased the expression of PC mRNA to 70%, 30% and 20%, respectively. Consistent with mRNA level, 10074-G5 at 10 μM minimally affected expression of PC expression at the protein level while at concentrations of 25 μM and 50 μM suppressed expression of PC protein by 80–90% (Fig. 2B). In contrast, 10074-G5 did not affect the expression of both PC mRNA and PC protein in MCF-7 cells (Fig. 2C and D). The lack of inhibitory effect of 10074-G5 on PC expression in MCF-7 cells was likely caused by lowered expression level of endogenous c-Myc. While inhibition of c-Myc-regulation of PC expression with 10 μM and 25 μM 10074-G5 did not affect growth of MDA-MB-231 cells, treatment of cells with 50 μM 10074-G5 resulted in 25% and 40% decrease in cell growth at days 2 and 3, respectively (Fig. 2E). Reference: Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165656. https://pubmed.ncbi.nlm.nih.gov/31874204/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 38.0 | 113.66 | |
| DMSO:PBS (pH 7.2) (1:4) | 0.2 | 0.6 | |
| DMF | 20.0 | 59.82 | |
| Ethanol | 6.0 | 17.95 |
The following data is based on the product molecular weight 334.335 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 |
| Formulation protocol: | 1. Lao-On U, Rojvirat P, Chansongkrow P, Phannasil P, Siritutsoontorn S, Charoensawan V, Jitrapakdee S. c-Myc directly targets an over-expression of pyruvate carboxylase in highly invasive breast cancer. Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165656. doi: 10.1016/j.bbadis.2019.165656. Epub 2019 Dec 23. PMID: 31874204. 2. Aksoz M, Albayrak E, Aslan GS, Turan RD, Alyazici LY, Siyah P, Tuysuz EC, Canikyan S, Yucel D, Meric N, Gulbas Z, Sahin F, Kocabas F. c-Myc Inhibitor 10074-G5 Induces Murine and Human Hematopoietic Stem and Progenitor Cell Expansion and HDR Modulator Rad51 Expression. Curr Cancer Drug Targets. 2019;19(6):479-494. doi: 10.2174/1568009618666180905100608. PMID: 30182856. |
| In vitro protocol: | 1. Lao-On U, Rojvirat P, Chansongkrow P, Phannasil P, Siritutsoontorn S, Charoensawan V, Jitrapakdee S. c-Myc directly targets an over-expression of pyruvate carboxylase in highly invasive breast cancer. Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165656. doi: 10.1016/j.bbadis.2019.165656. Epub 2019 Dec 23. PMID: 31874204. 2. Aksoz M, Albayrak E, Aslan GS, Turan RD, Alyazici LY, Siyah P, Tuysuz EC, Canikyan S, Yucel D, Meric N, Gulbas Z, Sahin F, Kocabas F. c-Myc Inhibitor 10074-G5 Induces Murine and Human Hematopoietic Stem and Progenitor Cell Expansion and HDR Modulator Rad51 Expression. Curr Cancer Drug Targets. 2019;19(6):479-494. doi: 10.2174/1568009618666180905100608. PMID: 30182856. |
| In vivo protocol: | TBD |
1: Zhang Y, Li J, Huang Y, Chen Y, Luo Z, Huang H, West RE 3rd, Nolin TD, Wang Z, Li S. Improved antitumor activity against prostate cancer via synergistic targeting of Myc and GFAT-1. Theranostics. 2023 Jan 1;13(2):578-595. doi: 10.7150/thno.76614. PMID: 36632215; PMCID: PMC9830436.
2: Zhang S, Hu Y, Wu Z, Zhou X, Wu T, Li P, Lian Q, Xu S, Gu J, Chen L, Wu G, Zhang T, Tang J, Xue J. Deficiency of Carbamoyl Phosphate Synthetase 1 Engenders Radioresistance in Hepatocellular Carcinoma via Deubiquitinating c-Myc. Int J Radiat Oncol Biol Phys. 2023 Apr 1;115(5):1244-1256. doi: 10.1016/j.ijrobp.2022.11.022. Epub 2022 Nov 22. PMID: 36423742.
3: Heller GT, Aprile FA, Michaels TCT, Limbocker R, Perni M, Ruggeri FS, Mannini B, Löhr T, Bonomi M, Camilloni C, De Simone A, Felli IC, Pierattelli R, Knowles TPJ, Dobson CM, Vendruscolo M. Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer's disease. Sci Adv. 2020 Nov 4;6(45):eabb5924. doi: 10.1126/sciadv.abb5924. PMID: 33148639; PMCID: PMC7673680.
4: Lao-On U, Rojvirat P, Chansongkrow P, Phannasil P, Siritutsoontorn S, Charoensawan V, Jitrapakdee S. c-Myc directly targets an over-expression of pyruvate carboxylase in highly invasive breast cancer. Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165656. doi: 10.1016/j.bbadis.2019.165656. Epub 2019 Dec 23. PMID: 31874204.
5: Wang H, Chauhan J, Hu A, Pendleton K, Yap JL, Sabato PE, Jones JW, Perri M, Yu J, Cione E, Kane MA, Fletcher S, Prochownik EV. Erratum: Disruption of Myc- Max Heterodimerization with Improved Cell-Penetrating Analogs of the Small Molecule 10074-G5. Oncotarget. 2018 Oct 12;9(80):35196. doi: 10.18632/oncotarget.26241. Erratum for: Oncotarget. 2013 Jun;4(6):936-47. PMID: 30416689; PMCID: PMC6205554.
6: Aksoz M, Albayrak E, Aslan GS, Turan RD, Alyazici LY, Siyah P, Tuysuz EC, Canikyan S, Yucel D, Meric N, Gulbas Z, Sahin F, Kocabas F. c-Myc Inhibitor 10074-G5 Induces Murine and Human Hematopoietic Stem and Progenitor Cell Expansion and HDR Modulator Rad51 Expression. Curr Cancer Drug Targets. 2019;19(6):479-494. doi: 10.2174/1568009618666180905100608. PMID: 30182856.
7: Kumar P, Yao LJ, Saidin S, Paleja B, van Loosdregt J, Chua C, Arkachaisri T, Consolaro A, Gattorno M, Martini A, Pischel KD, Williams GW, Lotz M, Albani S. Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis. J Autoimmun. 2018 Nov;94:90-98. doi: 10.1016/j.jaut.2018.07.014. Epub 2018 Aug 1. PMID: 30077426.
8: Wu C, Gupta N, Huang YH, Zhang HF, Alshareef A, Chow A, Lai R. Oxidative stress enhances tumorigenicity and stem-like features via the activation of the Wnt/β-catenin/MYC/Sox2 axis in ALK-positive anaplastic large-cell lymphoma. BMC Cancer. 2018 Apr 2;18(1):361. doi: 10.1186/s12885-018-4300-2. PMID: 29609590; PMCID: PMC5879562.
9: Wang H, Teriete P, Hu A, Raveendra-Panickar D, Pendelton K, Lazo JS, Eiseman J, Holien T, Misund K, Oliynyk G, Arsenian-Henriksson M, Cosford ND, Sundan A, Prochownik EV. Direct inhibition of c-Myc-Max heterodimers by celastrol and celastrol-inspired triterpenoids. Oncotarget. 2015 Oct 20;6(32):32380-95. doi: 10.18632/oncotarget.6116. PMID: 26474287; PMCID: PMC4741700.
10: Zhao Q, Assimopoulou AN, Klauck SM, Damianakos H, Chinou I, Kretschmer N, Rios JL, Papageorgiou VP, Bauer R, Efferth T. Inhibition of c-MYC with involvement of ERK/JNK/MAPK and AKT pathways as a novel mechanism for shikonin and its derivatives in killing leukemia cells. Oncotarget. 2015 Nov 17;6(36):38934-51. doi: 10.18632/oncotarget.5380. PMID: 26472107; PMCID: PMC4770748.
11: Wang H, Ramakrishnan A, Fletcher S, Prochownik EV. A quantitative, surface plasmon resonance-based approach to evaluating DNA binding by the c-Myc oncoprotein and its disruption by small molecule inhibitors. J Biol Methods. 2015;2(2):e18. doi: 10.14440/jbm.2015.54. PMID: 26280010; PMCID: PMC4537179.
12: Wang H, Sharma L, Lu J, Finch P, Fletcher S, Prochownik EV. Structurally diverse c-Myc inhibitors share a common mechanism of action involving ATP depletion. Oncotarget. 2015 Jun 30;6(18):15857-70. doi: 10.18632/oncotarget.4327. PMID: 26036281; PMCID: PMC4599242.
13: Kadioglu O, Fu Y, Wiench B, Zu Y, Efferth T. Synthetic cajanin stilbene acid derivatives inhibit c-MYC in breast cancer cells. Arch Toxicol. 2016 Mar;90(3):575-88. doi: 10.1007/s00204-015-1480-2. Epub 2015 Feb 26. PMID: 25716159.
14: Raffeiner P, Röck R, Schraffl A, Hartl M, Hart JR, Janda KD, Vogt PK, Stefan E, Bister K. In vivo quantification and perturbation of Myc-Max interactions and the impact on oncogenic potential. Oncotarget. 2014 Oct 15;5(19):8869-78. doi: 10.18632/oncotarget.2588. PMID: 25326649; PMCID: PMC4253403.
15: Chauhan J, Wang H, Yap JL, Sabato PE, Hu A, Prochownik EV, Fletcher S. Discovery of methyl 4'-methyl-5-(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-[1,1'-bip henyl]-3-carboxylate, an improved small-molecule inhibitor of c-Myc-max dimerization. ChemMedChem. 2014 Oct;9(10):2274-2285. doi: 10.1002/cmdc.201402189. Epub 2014 Jun 27. PMID: 24976143; PMCID: PMC4177309.
16: Müller I, Larsson K, Frenzel A, Oliynyk G, Zirath H, Prochownik EV, Westwood NJ, Henriksson MA. Targeting of the MYCN protein with small molecule c-MYC inhibitors. PLoS One. 2014 May 23;9(5):e97285. doi: 10.1371/journal.pone.0097285. PMID: 24859015; PMCID: PMC4032254.
17: Wang H, Chauhan J, Hu A, Pendleton K, Yap JL, Sabato PE, Jones JW, Perri M, Yu J, Cione E, Kane MA, Fletcher S, Prochownik EV. Disruption of Myc-Max heterodimerization with improved cell-penetrating analogs of the small molecule 10074-G5. Oncotarget. 2013 Jun;4(6):936-47. doi: 10.18632/oncotarget.1108. Erratum in: Oncotarget. 2018 Oct 12;9(80):35196. PMID: 23801058; PMCID: PMC3757250.
18: Gildea JJ, Tran HT, Van Sciver RE, Bigler Wang D, Carlson JM, Felder RA. A novel role for c-Myc in G protein-coupled receptor kinase 4 (GRK4) transcriptional regulation in human kidney proximal tubule cells. Hypertension. 2013 May;61(5):1021-7. doi: 10.1161/HYPERTENSIONAHA.111.00321. Epub 2013 Mar 18. PMID: 23509080; PMCID: PMC3640476.
19: Yap JL, Wang H, Hu A, Chauhan J, Jung KY, Gharavi RB, Prochownik EV, Fletcher S. Pharmacophore identification of c-Myc inhibitor 10074-G5. Bioorg Med Chem Lett. 2013 Jan 1;23(1):370-4. doi: 10.1016/j.bmcl.2012.10.013. Epub 2012 Oct 17. PMID: 23177256; PMCID: PMC3525812.
20: Velpula KK, Dasari VR, Tsung AJ, Dinh DH, Rao JS. Transcriptional repression of Mad-Max complex by human umbilical cord blood stem cells downregulates extracellular signal-regulated kinase in glioblastoma. Stem Cells Dev. 2012 Jul 1;21(10):1779-93. doi: 10.1089/scd.2011.0424. Epub 2011 Nov 21. Erratum in: Stem Cells Dev. 2013 May 15;22(10):1624. PMID: 21933022; PMCID: PMC3376458.
The c-Myc oncoprotein and its partner Max are intrinsically disordered (ID) monomers that undergo coupled folding and binding upon heterodimerization.
