10074-G5: Evidence-Based c-Myc Inhibitor for Cancer Research

Executive Summary: 10074-G5 is a small-molecule c-Myc inhibitor that blocks c-Myc/Max dimerization, a critical interaction in oncogenic transcriptional regulation (source: product_spec). The compound demonstrates an IC50 of 15.6 ± 1.5 μM in Daudi cells and 13.5 ± 2.1 μM in HL-60 cells under standard conditions (source: product_spec). In vivo, 20 mg/kg intravenous dosing for 10 days suppresses Daudi xenograft tumor growth in C.B-17 SCID mice without affecting body weight (source: product_spec). 10074-G5 is insoluble in water but is DMSO-soluble at ≥37.9 mg/mL, and it should be stored at -20°C with minimal long-term solution storage (source: product_spec). Overexpression of c-Myc is linked to tumor aggressiveness, including through the MYC/TERT/NFκB axis in multiple cancers (source: DOI).

Biological Rationale

c-Myc is a transcription factor within the bHLH-ZIP family, orchestrating cell proliferation, metabolism, differentiation, and apoptosis. Its overexpression is a hallmark of aggressive cancers, such as esophageal adenocarcinoma, where it drives disease progression through the MYC/TERT/NFκB signaling axis (source: DOI). Disruption of c-Myc/Max dimerization impedes oncogenic gene expression, offering a strategic target for tumor regression studies. APExBIO's 10074-G5 specifically targets this dimerization, providing a tool for dissecting c-Myc-dependent oncogenic pathways in translational research.

Mechanism of Action of 10074-G5

10074-G5 binds to c-Myc, preventing its dimerization with the Max protein, an essential step for DNA binding and transcriptional activation. This inhibition results in reduced c-Myc-driven gene expression, leading to cell cycle arrest and apoptosis in malignant cells. The effect is concentration-dependent, with measurable inhibition at 10 μM for c-Myc/Max dimerization and c-Myc protein reduction (source: product_spec). The compound's molecular structure (C18H12N4O3; MW 332.3) enables selective targeting of the c-Myc/Max interface. Mechanistically, this action interrupts downstream pathways implicated in tumor aggressiveness, such as the MYC/TERT/NFκB axis, which is upregulated in aggressive esophageal adenocarcinoma (source: DOI).

Evidence & Benchmarks

• 10074-G5 exhibits an IC50 of 15.6 ± 1.5 μM in Daudi cells, measured by cytotoxicity assay in vitro (source: product_spec).
• 10074-G5 demonstrates an IC50 of 13.5 ± 2.1 μM in HL-60 cells, confirming cross-line efficacy (source: product_spec).
• At 10 μM, the compound inhibits c-Myc/Max dimerization and reduces total c-Myc protein in cell-based assays (source: product_spec).
• In vivo, 20 mg/kg IV dosing for 10 days in C.B-17 SCID mice bearing Daudi xenograft tumors results in significant tumor growth suppression without impacting body weight (source: product_spec).
• c-Myc overexpression is associated with EMT, increased motility, and poor prognosis in esophageal adenocarcinoma, with MYC/TERT/NFκB signaling as a critical driver (source: DOI).

For further context, Targeting c-Myc in Cancer: Strategic Insights for 10074-G5 provides a mechanistic framework for deploying this inhibitor, while this article presents new product-specific benchmarks.

Applications, Limits & Misconceptions

10074-G5 is validated for use in apoptosis assays, cell cycle arrest studies, and tumor regression models across a spectrum of cancer cell types. Its DMSO-solubility facilitates robust experimental integration, though water insolubility restricts some protocols. Notably, in translational cancer models, 10074-G5 supports interrogation of c-Myc-driven oncogenesis, including MYC/TERT/NFκB axis modulation (source: DOI).

In 10074-G5 (SKU C5722): Practical Guidance for c-Myc Inhibition, readers find a scenario-driven evaluation of assay conditions. This review clarifies compound-specific reliability and solubility parameters, extending those findings with new quantitative evidence.

Common Pitfalls or Misconceptions

• 10074-G5 is not effective in water-based assays due to insolubility; DMSO or ethanol (with ultrasonic assistance) is required (source: product_spec).
• Long-term storage of 10074-G5 solutions is not recommended, as compound stability may be compromised (source: product_spec).
• 10074-G5 is not a pan-transcription factor inhibitor; specificity is limited to c-Myc/Max dimerization (source: workflow_recommendation).
• It is not suitable for clinical use; all data pertain to preclinical or in vitro models (source: workflow_recommendation).
• In vivo efficacy data are limited to select xenograft mouse models; results may not generalize to all tumor types or species (source: product_spec).

Workflow Integration & Parameters

Protocol Parameters

• apoptosis assay | 10 μM | Daudi, HL-60, other c-Myc dependent cell lines | Validated for c-Myc/Max dimerization inhibition and apoptosis induction | product_spec
• cell cycle arrest | 10–20 μM | Cancer cell lines with c-Myc overexpression | Enables G1/S transition blockade via c-Myc inhibition | product_spec
• tumor regression studies | 20 mg/kg IV, daily x10 days | C.B-17 SCID mice with Daudi xenografts | Demonstrates significant tumor growth suppression without weight loss | product_spec
• solution preparation | ≥37.9 mg/mL DMSO, ≥3.53 mg/mL ethanol (ultrasonic) | All in vitro uses | Ensures maximal solubility for consistent dosing | product_spec
• storage | -20°C (solid), minimal storage time for solutions | All research applications | Preserves compound integrity and activity | product_spec

For troubleshooting and workflow optimization, 10074-G5 c-Myc Inhibitor: Workflows & Troubleshooting in Cancer Research delivers practical guidance, while this article provides updated evidence-based parameters and limitations.

Conclusion & Outlook

10074-G5, supplied by APExBIO, is a rigorously validated small-molecule c-Myc inhibitor, enabling targeted disruption of c-Myc/Max dimerization in cancer research models. Its data-backed potency in both in vitro and in vivo systems supports its ongoing value for apoptosis, cell cycle, and tumor regression studies. While its specificity and solubility profile make it a preferred tool for mechanistic oncology research, users must adhere to recommended storage and solvent protocols to ensure reproducibility. The compound's utility is anchored in the elucidation of the c-Myc/TERT/NFκB axis, as demonstrated in aggressive esophageal adenocarcinoma and other malignancies (source: DOI). Future work will extend these findings to additional tumor models, but current data reinforce 10074-G5's role as a cornerstone small molecule for dissecting oncogenic c-Myc signaling.

To purchase or learn more, refer to the 10074-G5 product page.