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Updated: Feb 5, 2026
Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
Published on: July 26, 2017
Covalent CDK7 Inhibitor THZ1 Inhibits Myogenic Differentiation
Xinqi Ma1, Xielan Kuang1,2, Qing Xia1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou 510060, China.
Abstract:
Covalent CDK7 inhibitor THZ1 is a newly discovered anti-tumor drug.THZ1 affects the function of transcription factor TFIIH by inhibiting CDK7, which in turn affects RNA polymerase II, and ultimately affects transcription initiation. Study found that THZ1 could inhibit proliferation and promote apoptosis of several tumor cell lines. However, there is no report of the potential side effect of THZ1 in normal tissues. In the course of cancer, the muscle consumption of cachexia needs to be supplemented by the differentiation of muscle cells. However, the effect of THZ1 on myogenic differentiation remains unclear. Our study in this article found that THZ1 could both inhibit the differentiation of C2C12 cells and mouse primary myoblasts, also repressing the expression of differentiation-related transcription factors and muscle structural proteins, such as and myogenin, myh3 and MCK. Moreover, THZ1 could inhibit C2C12 cell proliferation and migration, increase its oxidative stress and promote its apoptosis. Our data indicates that THZ1 inhibits myogenic differentiation, suggesting that therapies based on THZ1 might have potential side effects on muscle functions.
Insights
The anti-tumor drug THZ1 inhibits cancer cell growth but also impairs muscle cell differentiation. This suggests potential muscle function side effects from THZ1-based cancer therapies.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- THZ1 is a novel covalent inhibitor of Cyclin-Dependent Kinase 7 (CDK7).
- CDK7 inhibition impacts transcription initiation by affecting TFIIH and RNA polymerase II.
- While effective against tumor cells, THZ1's effects on normal tissues, particularly muscle, are unknown.
Purpose of the Study:
- To investigate the impact of THZ1 on myogenic differentiation.
- To assess potential side effects of THZ1 on muscle cell function.
Main Methods:
- Utilized C2C12 cells and primary mouse myoblasts.
- Assessed myogenic differentiation markers (myogenin, myh3, MCK).
- Evaluated cell proliferation, migration, oxidative stress, and apoptosis.
Main Results:
- THZ1 significantly inhibited myogenic differentiation in both cell models.
- THZ1 repressed key differentiation-related transcription factors and muscle structural proteins.
- THZ1 also reduced C2C12 cell proliferation and migration, increased oxidative stress, and promoted apoptosis.
Conclusions:
- THZ1 demonstrates inhibitory effects on myogenic differentiation.
- These findings highlight potential adverse effects of THZ1-based therapies on muscle function.
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