| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Pyruvate dehydrogenase kinase (PDHK1 and PDHK2). TM-1 is a potent inhibitor of PDHK1 and PDHK2.
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|---|---|
| ln Vitro |
TM-1 (0-10 μM) has an IC50 value of 2.97 μM and an inhibition rate of 80.5% (dose 10 μM) when it comes to PDHK1 activity[1]. TM-1 (0-2.1 μM; 12 h) inhibits MG-63 cells with an EC50 value of 14.5 μM and has anti-osteosarcoma activity [1]. PDHC phosphorylation at Ser293 and Ser232 is dose-dependently reduced by TM-1 (3, 6, 12 μM; 24 hours) [1].
In vitro, TM-1 inhibits PDHK1 with an IC₅₀ of 2.97 μM and PDHK2 with an IC₅₀ of 5.2 μM. TM-1 blocks pyruvate dehydrogenase complex (PDHC) phosphorylation and inhibits cell proliferation. The compound is a potent 26S proteasome inhibitor and autophagy inducer. It significantly upregulates LC3-II levels and inhibits tumor cell proliferation by dual regulation of degradation pathways. TM-1 is used in multiple myeloma research. |
| ln Vivo |
In vivo, TM-1 has shown promise in preclinical studies as a potent inhibitor of key signaling pathways involved in tumor cell growth, survival, and metastasis. It is used in cancer research, particularly for multiple myeloma. Further details on in vivo efficacy are available in the primary research literature.
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| Enzyme Assay |
Non-cell enzyme assays for TM-1 are performed using purified PDHK1 and PDHK2 enzymes. PDHK activity is measured by the phosphorylation of pyruvate dehydrogenase (PDH) or a peptide substrate using [γ-³³P]ATP. Enzymes are incubated with the substrate, ATP, and varying concentrations of TM-1 (0.001-100 μM) in kinase buffer at 30°C for 30-60 minutes. The reaction is terminated, and phosphorylated substrate is quantified by filter binding or scintillation counting. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Cell viability assay [1]
Cell Types: MG-63 Cell Tested Concentrations: 3, 6, 12 μM Incubation Duration: 24 hrs (hours) Experimental Results: PDHK phosphorylation at Ser293 and Ser232 sites was Dramatically diminished at 6 or 12 μM concentration. Cellular assays for TM-1 are performed using cancer cell lines, particularly multiple myeloma cells. Cells are treated with TM-1 at concentrations ranging from 0.01-100 μM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. PDHC phosphorylation is assessed by Western blotting using phospho-specific antibodies. LC3-II levels are measured to assess autophagy induction. Cell cycle analysis is performed by flow cytometry. Apoptosis is evaluated by Annexin V staining. |
| Animal Protocol |
In vivo animal studies are conducted in mouse xenograft models using multiple myeloma or other cancer cell lines. Tumor-bearing mice are treated with TM-1 administered intraperitoneally or orally at doses determined from pharmacokinetic studies. Tumor volume is measured by calipers. At study termination, tumors are harvested for histology and biomarker analysis (e.g., PDHC phosphorylation, LC3-II levels). The compound's antitumor efficacy is assessed.
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| ADME/Pharmacokinetics |
TM-1 has a molecular weight of 468.55. It is a potent inhibitor of PDHK1 and PDHK2. The compound is soluble in DMSO. It is typically stored as a powder at -20°C. Further pharmacokinetic parameters such as half-life, clearance, and oral bioavailability would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for TM-1 are not available in the public domain. No significant toxicity has been reported at effective concentrations in preclinical studies. Standard safety pharmacology studies would be required for therapeutic development. The compound is for research use only.
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| References | |
| Additional Infomation |
TM-1 is a potent inhibitor of pyruvate dehydrogenase kinase (PDHK1 and PDHK2). It blocks pyruvate dehydrogenase complex phosphorylation and inhibits cell proliferation. TM-1 is used in multiple myeloma research. It is not approved for clinical use.
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| Molecular Formula |
C26H32N2O6
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|---|---|
| Molecular Weight |
468.54
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| Exact Mass |
468.226
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| CAS # |
921099-13-0
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| Related CAS # |
921099-13-0;1216759-24-8 (2HCl);
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| PubChem CID |
16424570
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| Appearance |
Off-white to light brown solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
34
|
| Complexity |
707
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)OC2=CC(OCCN3CCN(CCO)CC3)=CC=C2C(C)=C1C1=CC=C(OC)C(OC)=C1
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| InChi Key |
FJPOSFVCWXTUDP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H32N2O6/c1-18-21-6-5-20(33-15-13-28-10-8-27(9-11-28)12-14-29)17-23(21)34-26(30)25(18)19-4-7-22(31-2)24(16-19)32-3/h4-7,16-17,29H,8-15H2,1-3H3
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| Chemical Name |
3-(3,4-dimethoxyphenyl)-7-[2-[4-(2-hydroxyethyl)piperazin-1-yl]ethoxy]-4-methylchromen-2-one
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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: ~50 mg/mL (~106.7 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (12.5 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (12.5 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1.25 mg/mL (2.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (12.5 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1343 mL | 10.6714 mL | 21.3429 mL | |
| 5 mM | 0.4269 mL | 2.1343 mL | 4.2686 mL | |
| 10 mM | 0.2134 mL | 1.0671 mL | 2.1343 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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