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| Targets |
MYCMI-6 targets the MYC:MAX protein interaction. MYC is a transcription factor that is frequently dysregulated in various cancers, driving tumor cell proliferation, survival, and metabolism. MYC forms heterodimers with MAX to bind to DNA and activate transcription of target genes. By binding selectively to the MYC bHLHZip domain with a Kd of 1.6 μM, MYCMI-6 disrupts the MYC:MAX interaction, blocking MYC-driven transcription. This inhibition suppresses tumor cell growth and induces cell death in MYC-driven cancers.
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| ln Vitro |
MYCMI-6 (NSC354961) (6.25 μM; 48 hours) suppresses the development of tumor cells driven by MYC in an effective and precise manner [1]. Burkitt-located cells (Mutu, Daudi, and ST486) are another well-known example of MYC-driven malignancies. MYC easily localizes to one of the immunoglobulin sites in a dose-dependent manner, with an average GI50 of 0.5 μM. MYCMI-6 greatly slows the growth of these cells. Following a 24-hour treatment with MYCMI-6 for MCF7 cells, titration revealed a considerable reduction in the MYC:MAX isPLA signal, indicating that the IC50 of PLA inhibition of MYC:MAX versus MYCMI-6 was less than 1.5 μM. MYCMI-6 has an IC50 of 3.8 μM, which inhibits the production of MYC:MAX heterodimers. With an IC50, MYCMI-6 potently inhibits MYCN in neuroblasts. 7 percent. Tumor cell proliferation that is anchorage-independent has a GI50 value of less than 0.4 μM [1].
MYCMI-6 exhibits potent in vitro activity as a MYC:MAX interaction inhibitor. It selectively binds to the MYC bHLHZip domain with a Kd of 1.6 μM. The compound inhibits tumor cell growth in a MYC-dependent manner with IC50 concentrations as low as 0.5 μM. MYCMI-6 induces apoptosis in cancer cells. Importantly, the compound is not cytotoxic to normal human cells, indicating selectivity for cancer cells. These in vitro activities confirm its potential as an anticancer agent targeting the MYC oncogene. |
| ln Vivo |
In a MYC-requiring xenograft tumor model, MYCMI-6 (20 mg/kg; i.p.; once daily for 1-2 weeks) decreases tumor cell swelling, tumor microvessel density, and MYC:MAX interactions while inducing severe cellular ischemia.
In vivo activity of MYCMI-6 has been evaluated in animal models of MYC-driven cancers. The compound works by specifically targeting and disrupting the MYC protein's function, potentially suppressing tumor growth and inducing cell death. In vivo studies have demonstrated that MYCMI-6 inhibits tumor growth in MYC-dependent models. The compound's selectivity for MYC over MAX and its lack of cytotoxicity to normal cells suggest a favorable therapeutic window. Further studies are needed to fully characterize its pharmacokinetic and pharmacodynamic properties in vivo. |
| Enzyme Assay |
In vitro binding assays for MYCMI-6 involve measuring its affinity for the MYC bHLHZip domain. Surface plasmon resonance (SPR) or fluorescence polarization assays are typically used to determine the dissociation constant (Kd) of 1.6 μM. In these assays, recombinant MYC protein or the MYC bHLHZip domain is immobilized, and the compound is flowed over the surface to measure binding kinetics. Competitive binding assays with fluorescently labeled MYC peptides can also be used to confirm target engagement and calculate the IC50 for disruption of the MYC:MAX interaction.
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| Cell Assay |
Cell viability assay[1]
Cell Types: MYCN-amplified neuroblastoma cells (IMR-32, Kelly and SK-N-DZ), MYCN-non-amplified neuroblastoma cells (SK-N-F1, SK -N-AS and SK-N-RA) Tested Concentrations: 6.25 μM Incubation Duration: 48 hrs (hours) Experimental Results: The growth reduction of MYCN-amplified cell lines was Dramatically stronger than that of MYCN-amplified non-amplified cell lines. In vitro cellular assays for MYCMI-6 are conducted in cancer cell lines with MYC dysregulation, such as Burkitt's lymphoma, neuroblastoma, and other MYC-driven cancers. Cells are treated with varying concentrations of the compound, and cell proliferation is measured using MTT or CellTiter-Glo assays. MYC-driven transcription is assessed by measuring the expression of MYC target genes (e.g., cyclin D2, ornithine decarboxylase) by qPCR. Apoptosis is assessed by Annexin V staining or caspase activity assays. Cytotoxicity is assessed in normal human cells to confirm selectivity. |
| Animal Protocol |
Animal/Disease Models: 6-8 weeks old athymic nude mice (SK-N-DZ neuroblastoma cells carrying MYCN amplification) [1]
Doses: 20mg/kg body weight Route of Administration: Ip; effect [1]. one time/day for 1-2 weeks Experimental Results: There was a significant increase in the expansion of apoptotic areas and a significant increase in non-proliferative areas in the tumors as determined by Ki67 staining in the tumors. In vivo animal experiments with MYCMI-6 are conducted in mouse xenograft models of MYC-driven cancers. Immunodeficient mice are engrafted with cancer cell lines harboring MYC dysregulation. MYCMI-6 is administered via intraperitoneal injection or oral gavage at varying doses. Tumor growth is measured over time, and tumor tissues are harvested for analysis of MYC target gene expression, apoptosis markers, and MYC protein levels. Pharmacodynamic studies are performed to confirm target engagement and inhibition of MYC-driven transcription. These studies evaluate the compound's efficacy and mechanism of action in vivo. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for MYCMI-6 are limited. The compound has a molecular weight of 373.41 and is soluble in DMSO. Its bioavailability and half-life have not been extensively characterized. The compound is typically stored at -20°C. As a research compound, MYCMI-6 is primarily used in vitro and in cell-based assays. Further PK studies would be needed to support advanced preclinical development. The compound should be handled with appropriate laboratory safety precautions.
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| Toxicity/Toxicokinetics |
MYCMI-6 is considered to have low toxicity based on its use as a research compound and its lack of cytotoxicity to normal human cells. However, comprehensive toxicological evaluations have not been extensively published. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound. Further toxicity studies would be required to support any potential clinical development.
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| References | |
| Additional Infomation |
MYCMI-6 is a potent and selective endogenous inhibitor of MYC:MAX protein interactions. It is also known as NSC354961. The compound selectively binds to the MYC bHLHZip domain with a Kd of 1.6 μM. MYCMI-6 blocks MYC-driven transcription and inhibits tumor cell growth in a MYC-dependent manner. It induces apoptosis and is not cytotoxic to normal human cells. The compound is available in high purity (98%) for research applications. Its selectivity for MYC makes it a valuable tool for studying MYC-driven cancers and for developing new cancer therapies.
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| Molecular Formula |
C20H19N7O
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| Molecular Weight |
373.411
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| Exact Mass |
373.165
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| CAS # |
681282-09-7
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| Related CAS # |
1093100-07-2 (2HCl);681282-09-7;
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| PubChem CID |
434695
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
547
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| Defined Atom Stereocenter Count |
0
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| SMILES |
NC1C2=C(C=C(/N=N/C3=CC=C(N)N=C3N)C=C2)N=C2C=1C=C(OCC)C=C2
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| InChi Key |
QNWGRUNKGVWOTA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19N7O/c1-2-28-12-4-6-15-14(10-12)19(22)13-5-3-11(9-17(13)24-15)26-27-16-7-8-18(21)25-20(16)23/h3-10H,2H2,1H3,(H2,22,24)(H4,21,23,25)
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| Chemical Name |
3-[(9-amino-7-ethoxyacridin-3-yl)diazenyl]pyridine-2,6-diamine
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| Synonyms |
MYCMI6; MYCMI 6
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~2.4 mg/mL (~6.43 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6780 mL | 13.3901 mL | 26.7802 mL | |
| 5 mM | 0.5356 mL | 2.6780 mL | 5.3560 mL | |
| 10 mM | 0.2678 mL | 1.3390 mL | 2.6780 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.
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