IMT1B (Synonyms: LDC203974) |
Catalog No.GC62446
One-Click Copy Product Info
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IMT1B is a highly specific inhibitor of mitochondrial RNA polymerase (POLRMT), inhibiting mitochondrial gene expression.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2304621-06-3
Sample solution is provided at 25 µL, 10mM.
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IMT1B is a highly specific inhibitor of mitochondrial RNA polymerase (POLRMT), inhibiting mitochondrial gene expression[1]. IMT1B dose-dependently reduces mitochondrial DNA transcription levels, leading to dysfunction of OXPHOS protein complexes and cellular energy crisis, inhibiting a variety of cancer cells [2]. IMT1B has been widely used in cell models to regulate mitochondrial DNA transcription for altering the sensitivity to radiotherapy[3].
In vitro, IMT1B treatment for 168 hours significantly inhibited the proliferation of A2780, MDA-MB-468 and HeLa cells, and the IC50 values were 0.138 ± 0.015, 0.189 ± 0.015, and 1.052 ± 0.154μM, respectively[4]. The 72-hour treatment with 1µM IMT1B increased the sensitivity of chemo-resistant HCT116 cells to 5-fluorouracil, inhibited mitochondrial DNA transcription in the cells, without affecting the expression level of HOXC11[5]. IMT1B treatment at 2.5µM for 24 hours significantly reduced the phosphorylation levels of IRF3 and STAT1 in wild-type A375 cells induced by caspase-independent cell death, and inhibited the expression of ISG15 and IFIT3 transcripts[6]. 0.2µM of IMT1B pretreatment for 1 hour can effectively reduce the dsRNA level in nucleus pulposus cells, decrease the levels of CCL2/7 in the cells, and down-regulate the expressions of p-PKR/PKR, p-eIF2α/eIF2α and ATF4[7].
In vivo, IMT1B treatment (100mg/kg; p.o.) for 27 days could significantly reduce the tumor volume in a xenograft mouse model of A2780 cells, and decrease the mitochondrial DNA transcription level as well as the expression level of respiratory chain subunits in the tumors[1]. In the mouse model of liver ischemia-reperfusion injury, a single intravenous injection of 1mg/kg IMT1B for 24 hours significantly resulted in a significant decrease in the necrotic area of liver tissue in mice, accompanied by a decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels[8].
References:
[1] Bonekamp N A, Peter B, Hillen H S, et al. Small-molecule inhibitors of human mitochondrial DNA transcription[J]. Nature, 2020, 588(7839): 712-716.
[2] Yu H J, Xiao G L, Zhao Y Y, et al. Targeting mitochondrial metabolism and RNA polymerase POLRMT to overcome multidrug resistance in cancer[J]. Frontiers in Chemistry, 2021, 9: 775226.
[3] Li G, Lin X, Wang X, et al. Enhancing radiosensitivity in triple-negative breast cancer through targeting ELOB[J]. Breast Cancer, 2024, 31(3): 426-439.
[4] Li X, Ze X, Zhou S, et al. Discovery of a novel, potent, orally active, and safe inhibitor targeting human mitochondrial RNA polymerase[J]. Journal of Medicinal Chemistry, 2023, 66(7): 5118-5153.
[5] Chu S, Ren X, Cao L, et al. HOXC11-mediated regulation of mitochondrial function modulates chemoresistance in colorectal cancer[J]. BMC cancer, 2024, 24(1): 921.
[6] Killarney S T, Washart R, Soderquist R S, et al. Executioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis[J]. Nature Communications, 2023, 14(1): 1399.
[7] Tian S, Chen X, Wu W, et al. Nucleus pulposus cells regulate macrophages in degenerated intervertebral discs via the integrated stress response-mediated CCL2/7-CCR2 signaling pathway[J]. Experimental & molecular medicine, 2024, 56(2): 408-421.
[8] Wu C, Miao H, Yi Z, et al. STING-mediated mitochondrial DNA release exacerbates PANoptosis in liver ischemia reperfusion injury[J]. International Immunopharmacology, 2025, 157: 114778.
| Cell experiment [1]: | |
Cell lines | A2780 cells |
Preparation Method | The A2780 cells were cultured in Dulbecco’s modified Eagle medium (DMEM) containing 1g/L glucose, supplemented with 10% (v/v) fetal bovine serum (FBS) and antibiotics (penicillin-streptomycin). The cells were cultured in a humidified cell incubator at 37°C and 5% CO2. The single cells in the A2780 cell suspension were sorted into 96-well cell culture plates. Subsequently, five different cell clones were cultured to confluence. Different concentrations (0.001, 0.01, 0.1, 1.0, 10μM) of IMT1B were used for treatment. The cells were incubated with DMSO or in the presence of IMT1B for 168 hours, and cell viability was determined. |
Reaction Conditions | 0.001, 0.01, 0.1, 1.0, 10μM; 168h |
Applications | IMT1B treatment reduced the cell viability of A2780 cells in a concentration-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female blab/c mice |
Preparation Method | Female blab/c mice (18 to 22g, 4 to 5 weeks of age) were subcutaneously inoculated with a total of 1 × 106 A2780 cells on the right side to initiate tumor growth. When the mean tumor volume reached approximately 100mm3, the mice were randomly divided into four groups (n =6 each). IMT1B or compound D26 was dissolved in 25% PEG400 and 30% hydroxypropyl-β-cyclodextrin aqueous solution as a vehicle. IMT1B and compound D26 were orally administered at the doses of 100mg/kg/day for 27 days. Tumor size and body weight were measured every 2 days. Tumor volume was calculated as tumor volume (mm3) = (length × width2)/2. |
Dosage form | 100mg/kg/day for 27 days; p.o. |
Applications | IMT1B significantly inhibited tumor volume and weight without affecting body weight in mice. |
References: | |
| Cas No. | 2304621-06-3 | SDF | |
| Synonyms | LDC203974 | ||
| Formula | C24H21ClFNO6 | M.Wt | 473.88 |
| Solubility | DMSO : 250 mg/mL (527.56 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1102 mL | 10.5512 mL | 21.1024 mL |
| 5 mM | 422 μL | 2.1102 mL | 4.2205 mL |
| 10 mM | 211 μL | 1.0551 mL | 2.1102 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 27 reference(s) in Google Scholar.)