Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
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Updated: Nov 19, 2025
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Justyna Magdalena Hermanowicz1,2, Anna Szymanowska3, Beata Sieklucka1
1Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland.
Abstract:
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. The impact of the new pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide (MM-129) was evaluated against human colon cancer in vitro and in zebrafish xenografts. Our results show that this new synthesised compound effectively inhibits cell survival in BTK-dependent mechanism. Its effectiveness is much higher at a relatively low concentration as compared with the standard chemotherapy used for CRC, i.e. 5-fluorouracil (5-FU). Flow cytometry analysis after annexin V-FITC and propidium iodide staining revealed that apoptosis was the main response of CRC cells to MM-129 treatment. We also found that MM-129 effectively inhibits tumour development in zebrafish embryo xenograft model, where it showed a markedly synergistic anticancer effect when used in combination with 5-FU. The above results suggest that this novel heterofused 1,2,4-triazine derivative may be a promising candidate for further evaluation as chemotherapeutic agent against CRC.
Insights
A novel compound, MM-129, shows significant promise in treating colorectal cancer (CRC) by inhibiting cell survival and inducing apoptosis. It is more effective than 5-fluorouracil and synergistic with it in preclinical models.
Area of Science:
- Oncology
- Medicinal Chemistry
- Pharmacology
Background:
- Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
- There is a need for novel therapeutic agents with improved efficacy and reduced toxicity compared to current treatments like 5-fluorouracil (5-FU).
Purpose of the Study:
- To evaluate the anticancer potential of a novel pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide (MM-129) against colorectal cancer.
- To investigate the mechanism of action and efficacy of MM-129 in vitro and in vivo models.
Main Methods:
- In vitro studies using human colon cancer cell lines.
- Zebrafish xenograft models for in vivo evaluation.
- Flow cytometry for apoptosis analysis.
- Combination studies with 5-fluorouracil (5-FU).
Main Results:
- MM-129 demonstrated potent inhibition of colorectal cancer cell survival via a BTK-dependent mechanism.
- MM-129 exhibited superior efficacy compared to 5-FU at equivalent concentrations.
- Apoptosis was identified as the primary mode of cell death induced by MM-129.
- MM-129 significantly inhibited tumor development in zebrafish xenografts and showed synergistic effects with 5-FU.
Conclusions:
- The novel compound MM-129 possesses significant anticancer activity against colorectal cancer.
- MM-129 represents a promising candidate for further development as a chemotherapeutic agent for CRC.
- Combination therapy with 5-FU may enhance treatment outcomes for colorectal cancer.
