10074-G5

Names

[ Name ]:
10074-G5

[Synonym ]:
N-[1,1 inverted exclamation marka-Biphenyl-2-yl]-7-nitro-2,1,3-Benzoxadiazol-4-amine
N-2-Biphenylyl-7-nitro-2,1,3-benzoxadiazol-4-amine
2,1,3-Benzoxadiazol-4-amine, N-[1,1'-biphenyl]-2-yl-7-nitro-
N-(2-Biphenylyl)-7-nitro-2,1,3-benzoxadiazol-4-amine
Biphenyl-2-yl-(7-nitro-benzo[1,2,5]oxadiazol-4-yl)-amine
7-nitro-N-(2-phenylphenyl)-2,1,3-benzoxadiazol-4-amine
10074-G5

Biological Activity

[Description]:

10074-G5 is an inhibitor of c-Myc-Max dimerization with an IC50 of 146 μM.

[Related Catalog]:

Signaling Pathways >> Apoptosis >> c-Myc

Research Areas >> Cancer

[Target]

IC50: 15.6 μM (Daudi cells), 13.5 μM (HL-60 cells)[1], 146 μM (c-Myc–Max)[2]

[In Vitro]

10074-G5 inhibits the growth of Daudi Burkitt's lymphoma cells and disruptes c-Myc/Max dimerization. The IC50 values against Daudi and HL-60 cells are 15.6 and 13.5 μM, respectively[1]. 10074-G5 binds the Myc peptide Myc353-437 with a Kd value of 2.8 μM in the region Arg363-Ile381. 10074-G5 binds in a cavity that is created by a kink (Asp379-Ile381) in the N-terminus of an induced helical domain (Leu370–Arg378)[3].

[In Vivo]

The plasma half-life of 10074-G5 in mice treated with 20 mg/kg i.v. is 37 min, and peak plasma concentration was 58 μM, which is 10-fold higher than peak tumor concentration[1].

[Cell Assay]

10074-G5 is dissolved in DMSO and diluted with culture medium. Daudi cells or HL-60 cells in logarithmic growth are treated with 10074-G5 (1-100 μM). After 72 h, 50 μL of 1 mg/mL MTT is added to each well and incubated for 4 h. At the end of the incubation, medium containing drug and MTT is removed from each well, and 100 μl of DMSO is added, followed by shaking for 5 min. The absorbance at 570 nm is read[1].

[Animal admin]

Mice: C.B-17 SCID mice bearing Daudi xenografts are stratified into the following groups (10 mice/group): control; vehicle control (0.01 ml/g body weight, once daily for 5 days); positive control, doxorubicin (2.5 mg/kg/dose, one dose every 4 days for three doses); and 10074-G5 (20 mg/kg/dose, once daily for 5 days). Mice are dosed intravenously on the appropriate schedule, and body weights and tumor volumes are recorded twice weekly[1].

[References]

[1]. Clausen DM, et al. In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc/Max dimerization. J Pharmacol Exp Ther. 2010 Dec;335(3):715-27.

[2]. Chauhan J, et al. Discovery of methyl 4'-methyl-5-(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-[1,1'-biphenyl]-3-carboxylate, an improved small-molecule inhibitor of c-Myc-max dimerization. ChemMedChem. 2014 Oct;9(10):2274-85.

[3]. Yap JL, et al. Pharmacophore identification of c-Myc inhibitor 10074-G5. Bioorg Med Chem Lett. 2013 Jan 1;23(1):370-4.

[Related Small Molecules]

10058-F4 | KJ Pyr 9 | ML327 | Mycro 3 | KSI-3716

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
538.6±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₈H₁₂N₄O₃

[ Molecular Weight ]:
332.313

[ Flash Point ]:
279.5±32.9 °C

[ Exact Mass ]:
332.090942

[ PSA ]:
96.77000

[ LogP ]:
4.97

[ Vapour Pressure ]:
0.0±1.4 mmHg at 25°C

[ Index of Refraction ]:
1.719

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H315-H319-H335

[ Precautionary Statements ]:
P261-P301 + P310-P305 + P351 + P338

[ RIDADR ]:
UN 2811 6.1 / PGIII

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

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 6 , 38934-51, (2015)

Leukemia remains life-threatening despite remarkable advances in chemotherapy. The poor prognosis and drug resistance are challenging treatment. Novel drugs are urgently needed. Shikonin, a natural na...

In vivo quantification and perturbation of Myc-Max interactions and the impact on oncogenic potential.

Oncotarget 5(19) , 8869-78, (2014)

The oncogenic bHLH-LZ transcription factor Myc forms binary complexes with its binding partner Max. These and other bHLH-LZ-based protein-protein interactions (PPI) in the Myc-Max network are essentia...

Structurally diverse c-Myc inhibitors share a common mechanism of action involving ATP depletion.

Oncotarget 6 , 15857-70, (2015)

The c-Myc (Myc) oncoprotein is deregulated in a large proportion of diverse human cancers. Considerable effort has therefore been directed at identifying pharmacologic inhibitors as potential anti-neo...