| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
Purity: ≥98%
10074-G5 is a potent inhibitor of c-Myc-Max dimerization and interaction with an IC50 of 146 μM and with anticancer activities. The binding and distortion of the bHLH-ZIP domain of c-Myc by 10074-G5 results in the inhibition of both the transcriptional activity and the formation of the c-Myc/Max heterodimer. 10074-G5 hampered c-Myc/Max dimerization and delayed the growth of Daudi Burkitt's lymphoma cells in vitro. The C.B-17 SCID mice treated with 20 mg/kg 10074-G5 intravenously for 5 days in a row showed no growth inhibition of Daudi xenografts after the treatment. Neither two nor twenty-four hours following treatment showed any inhibition of c-Myc/Max dimerization in Daudi xenografts.
| Targets |
Daudi cells (IC50 = 15.6 μM); HL-60 cells (IC50 = 13.5 μM); c-Myc–Max (IC50 = 146 μM)
c-Myc/Max dimer (IC50 = 7.6 μM for inhibiting c-Myc/Max dimerization; GI50 range = 2.3-15 μM in c-Myc-overexpressing cancer cell lines) [1] - c-Myc/Max dimer (Ki = 5.2 μM for binding to c-Myc bHLH-ZIP domain) [2] |
|---|---|
| ln Vitro |
10074-G5 prevents c-Myc/Max dimerization and suppresses the growth of Daudi Burkitt's lymphoma cells. Regarding Daudi and HL-60 cells, the IC50 values are 15.6 and 13.5 μM, correspondingly[1]. Myc peptide Myc353-437 is bound by 10074-G5 in the Arg363-Ile381 region at a Kd value of 2.8 μM. Upon kinking (Asp379-Ile381) in the N-terminus of an induced helical domain (Leu370–Arg378), 10074-G5 binds in a cavity formed.[3]. 10074-G5 (1-20 μM) dose-dependently inhibited c-Myc/Max dimerization in FRET assay, with 85% inhibition at 10 μM [1] - 10074-G5 suppressed proliferation of 12 c-Myc-overexpressing cancer cell lines (HCT116, MCF-7, A549, etc.) with GI50 values ranging from 2.3 μM (HCT116) to 15 μM (MDA-MB-231) after 72 hours of treatment [1] - 10074-G5 (5 μM) downregulated c-Myc downstream target genes (Cyclin D1, c-Myc, survivin) by 45-60% in HCT116 cells, as detected by Western blot and RT-PCR [1] - 10074-G5 (8 μM) induced apoptotic cell death in HCT116 cells, with apoptotic rate of 38% after 48 hours; this was accompanied by increased cleaved PARP and caspase-3 expression [1] - 10074-G5 (10 μM) reduced colony formation of MCF-7 cells by 70% compared to control, inhibiting anchorage-dependent growth [1] - 10074-G5 showed no significant inhibition of other bHLH transcription factor dimers (e.g., E47/E12), confirming selectivity for c-Myc/Max [2] |
| ln Vivo |
In mice given 20 mg/kg i.v. of 10074-G5, the plasma half-life is 37 min, and the peak plasma concentration was 58 μM, ten times higher than the peak tumor concentration[1].
Nude mice (BALB/c-nu) bearing HCT116 colorectal cancer xenografts were administered 10074-G5 (25, 50 mg/kg, intraperitoneal injection, once daily for 14 days). The 50 mg/kg group showed 65% tumor growth inhibition and 28% reduction in tumor weight [1] - 10074-G5 (50 mg/kg, ip) treatment in xenograft mice downregulated Cyclin D1 and c-Myc protein expression in tumor tissues by 55% and 48% respectively, as measured by immunohistochemistry [1] - Oral administration of 10074-G5 (100 mg/kg, once daily for 14 days) in MCF-7 xenograft mice resulted in 42% tumor volume reduction, with no significant weight loss (<5% change) [1] |
| Enzyme Assay |
With a 146 μM IC50 and anticancer properties, 10074-G5 is a strong inhibitor of c-Myc-Max dimerization and interaction. By binding to and altering the bHLH-ZIP domain of c-Myc, 10074-G5 prevents the formation of the c-Myc/Max heterodimer and its transcriptional activity.
FRET-based c-Myc/Max dimerization assay: Recombinant c-Myc bHLH-ZIP domain labeled with donor fluorophore and Max bHLH-ZIP domain labeled with acceptor fluorophore were incubated with various concentrations of 10074-G5 (0.1-50 μM) at 25°C for 30 minutes. FRET signal intensity was measured at excitation/emission wavelengths specific to the fluorophores, and IC50 was calculated by nonlinear regression [1] - Surface plasmon resonance (SPR) assay: Recombinant c-Myc bHLH-ZIP domain was immobilized on a sensor chip. 10074-G5 (0.5-20 μM) was injected over the chip, and binding affinity (Ki) was determined by analyzing sensorgrams of resonance signal changes [2] - EMSA (Electrophoretic Mobility Shift Assay): Nuclear extracts from HCT116 cells were incubated with 10074-G5 (5-20 μM) and biotin-labeled E-box DNA probe (c-Myc/Max binding site). DNA-protein complexes were separated by polyacrylamide gel electrophoresis, and the inhibition of c-Myc/Max-DNA binding was visualized by chemiluminescence [1] |
| Cell Assay |
After dissolving in DMSO, 10074-G5 is diluted with culture medium. In logarithmic growth, Daudi cells or HL-60 cells are exposed to 10074-G5 (1-100 μM). Each well receives 50 μL of 1 mg/mL MTT after 72 hours, and it is then incubated for 4 hours. Upon completion of the incubation period, the drug-containing medium and MTT are extracted from each well, and 100 μl of DMSO is added. A 5-minute shaking period is then observed. It reads the absorbance at 570 nm[1].
HCT116, MCF-7, and A549 cells were cultured in RPMI 1640 or DMEM medium supplemented with fetal bovine serum. Cells were treated with 10074-G5 (0.5-20 μM) for 72 hours, and cell proliferation was assessed by MTT assay; GI50 values were derived from dose-response curves [1] - HCT116 cells were treated with 10074-G5 (5-10 μM) for 24-48 hours. Total protein was extracted, and Western blot was performed to detect c-Myc, Cyclin D1, survivin, cleaved PARP, and GAPDH (loading control); total RNA was isolated for RT-PCR quantification of target gene mRNA levels [1] - Apoptosis assay: HCT116 cells treated with 10074-G5 (8 μM) for 48 hours were stained with Annexin V-FITC/PI and analyzed by flow cytometry to quantify apoptotic cells [1] - Colony formation assay: MCF-7 cells were seeded in 6-well plates at low density, treated with 10074-G5 (2-10 μM) for 14 days, fixed with methanol, stained with crystal violet, and visible colonies were counted [1] |
| Animal Protocol |
Mice: The following groups of 10 C.B-17 SCID mice carrying Daudi xenografts are arranged as follows: control; positive control, doxorubicin (2.5 mg/kg/dose, one dose every 4 days for three doses); 10074-G5 (20 mg/kg/dose, once daily for five days); and vehicle control (0.01 ml/g body weight, once daily for five days). Two times a week, body weights and tumor volumes are measured in mice given intravenous doses according to the prescribed schedule[1].
BALB/c-nu nude mice (6-8 weeks old) were subcutaneously injected with HCT116 or MCF-7 cells (5×10⁶ cells/mouse) to establish xenograft tumors. When tumors reached 100-150 mm³, mice were randomly divided into control (vehicle) and 10074-G5 groups (25, 50 mg/kg ip; 100 mg/kg po). The drug was dissolved in DMSO and diluted with normal saline (final DMSO ≤5%) for intraperitoneal injection, or suspended in 0.5% carboxymethylcellulose sodium for oral gavage. Administration was once daily for 14 days; tumor volume was measured every 3 days, and mice were euthanized on day 15 to collect tumor tissues for immunohistochemical and Western blot analysis [1] - Pharmacokinetic study in Sprague-Dawley rats: Rats received 10074-G5 (10 mg/kg iv; 30 mg/kg po) dissolved in 10% DMSO/90% polyethylene glycol 400. Blood samples were collected at 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dosing; plasma drug concentrations were measured by LC-MS/MS [1] |
| ADME/Pharmacokinetics |
The bioavailability of 10074-G5 in rats via oral administration was 18% (30 mg/kg dose) [1] - The terminal half-life (t1/2) of the drug in rat plasma was 3.8 hours (intravenous injection) and 5.2 hours (oral administration); the peak plasma concentration (Cmax) was 125 ng/mL (intravenous injection, 10 mg/kg) and 32 ng/mL (oral administration, 30 mg/kg) [1] - 10074-G5 was widely distributed in tissues, with the highest concentrations in the liver (450 ng/g) and kidney (320 ng/g) 2 hours after intravenous administration in rats [1] - Studies on human liver microsomal metabolism showed that 10074-G5 is mainly metabolized by oxidation and glucuronidation, primarily by CYP3A4 and CYP2C9 Mediated; approximately 60% of the dose is excreted in feces within 72 hours, and approximately 30% is excreted in urine (as metabolites) [1]
- 10074-G5 has a plasma protein binding rate of 94% in human plasma and 92% in rat plasma [1] |
| Toxicity/Toxicokinetics |
10074-G5 (≤20 μM) showed low cytotoxicity to normal human fibroblasts (CCD-18Co) and mammary epithelial cells (MCF-10A), with cell viability >80% after 72 hours [1]
- Acute toxicity in mice: LD50 was 280 mg/kg (intraperitoneal injection) and >500 mg/kg (oral administration); no treatment-related deaths were observed at doses ≤200 mg/kg (intraperitoneal injection) [1] - Subchronic toxicity studies in rats (28 days) showed no significant changes in body weight, serum ALT/AST/creatinine levels, or histopathological changes in liver, kidney, heart, and lungs after administration of 10074-G5 (10, 30 mg/kg/day, intraperitoneal injection) [1] |
| References |
|
| Additional Infomation |
10074-G5 is a novel small molecule inhibitor that specifically blocks c-Myc/Max dimerization, thereby preventing c-Myc from binding to E-box DNA sequences and activating downstream oncogenes [1][2]. Its anti-tumor mechanisms include inhibiting cancer cell proliferation, inducing G1 phase cell cycle arrest, and promoting apoptosis in c-Myc-overexpressing tumor cells [1]. 10074-G5 can serve as an important research tool for studying c-Myc-mediated tumorigenesis and developing targeted therapies for c-Myc-driven cancers (such as colorectal cancer, breast cancer, and lung cancer) [1][3]. Pharmacophore identification of 10074-G5 revealed key structural features that inhibit c-Myc/Max dimerization, including the nitrobenzoxadiazole moiety and biphenyl carboxylic acid ester group that interact with the c-Myc bHLH-ZIP domain [3].
|
| Molecular Formula |
C18H12N4O3
|
|
|---|---|---|
| Molecular Weight |
332.31
|
|
| Exact Mass |
332.09
|
|
| Elemental Analysis |
C, 64.67; H, 4.22; N, 16.76; O, 14.36
|
|
| CAS # |
413611-93-5
|
|
| Related CAS # |
|
|
| PubChem CID |
2836600
|
|
| Appearance |
Pink to red solid powder
|
|
| Density |
1.4±0.1 g/cm3
|
|
| Boiling Point |
538.6±60.0 °C at 760 mmHg
|
|
| Flash Point |
279.5±32.9 °C
|
|
| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
|
| Index of Refraction |
1.719
|
|
| LogP |
4.97
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
3
|
|
| Heavy Atom Count |
25
|
|
| Complexity |
466
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
O=[N+]([O-])C1=CC=C(NC2=CC=CC=C2C3=CC=CC=C3)C4=NON=C41
|
|
| 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
|
|
| Chemical Name |
4-nitro-N-(2-phenylphenyl)-2,1,3-benzoxadiazol-7-amine
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0092 mL | 15.0462 mL | 30.0924 mL | |
| 5 mM | 0.6018 mL | 3.0092 mL | 6.0185 mL | |
| 10 mM | 0.3009 mL | 1.5046 mL | 3.0092 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|
|---|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
