| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
CDK1 Caspase-9 MCL1
TC11 targets MCL1 (myeloid cell leukemia-1), a member of the BCL-2 family that promotes cell survival. It induces the degradation of MCL1, leading to the induction of apoptosis during prolonged mitotic arrest. Additionally, TC11 activates caspase-9 and CDK1, which are involved in the apoptotic pathway and cell cycle regulation. This multi-target mechanism contributes to its potent anti-cancer activity. |
|---|---|
| ln Vitro |
In KMS34 cells, TC11 (0~30 μM; 24 hours) causes cell death[1]. TC11 (5 μM; 0~48 hours; KMS34 cells) causes M arrest and downregulates MCL1 expression as well as an apoptotic pathway that leads to cell death[1].
In vitro, TC11 induces degradation of MCL1, leading to apoptotic death during prolonged mitotic arrest. It activates caspase-3, -8, and -9, indicating the induction of apoptosis. The compound inhibits tumor cell proliferation and induces apoptosis in multiple myeloma cells. Its activity is mediated through the degradation of MCL1 and activation of caspases, resulting in cell cycle arrest and cell death. |
| ln Vivo |
In vivo, TC11 has shown activity against multiple myeloma cell line KMS34 tumor xenografts in ICR/SCID mice. This demonstrates its potential for treating multiple myeloma. The compound's efficacy in vivo is likely due to its ability to degrade MCL1 and induce apoptosis in tumor cells. Further studies are needed to fully characterize its in vivo activity.
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| Enzyme Assay |
Specific in vitro enzyme/receptor binding assay protocols for TC11 are not detailed. As a MCL1 degrader, its activity is typically assessed by measuring MCL1 protein levels in cells treated with the compound. The compound's ability to activate caspases and CDK1 is also evaluated. These cell-based assays are crucial for confirming its mechanism of action.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: KMS34 cells Tested Concentrations: 0~30 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced cell death. Western Blot Analysis[1] Cell Types: KMS34 cells Tested Concentrations: 5 μM Incubation Duration: 0~48 hrs (hours) Experimental Results: Induced cell death occurs through an apoptotic pathway and downregulated MCL1 expression. Cell Cycle Analysis[1] Cell Types: KMS34 cells Tested Concentrations: 5 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced M arrest. Cellular assays for TC11 are performed using multiple myeloma cell lines, such as KMS34. Cells are treated with varying concentrations of the compound, and MCL1 degradation is assessed by Western blotting. Apoptosis is measured by caspase activation assays and cell viability assays. These experiments confirm the compound's potency and mechanism of action. |
| Animal Protocol |
In vivo animal protocols for TC11 involve the use of ICR/SCID mice bearing KMS34 tumor xenografts. The compound is administered to tumor-bearing mice, and tumor growth is monitored. The study evaluates the compound's efficacy in reducing tumor volume. These xenograft models are standard for assessing the antitumor activity of TC11.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of TC11 have not been characterized. It is a small molecule with a molecular weight of 322.40. The compound is typically dissolved in DMSO for in vitro studies. Further studies are needed to determine its oral bioavailability, half-life, and tissue distribution. Its potential as an orally available anticancer agent would require optimization of its PK properties.
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| Toxicity/Toxicokinetics |
Toxicity data for TC11 are limited. As a MCL1 degrader, it may have on-target toxicities related to the essential role of MCL1 in normal cell survival. The compound is intended for research use only and is not approved for human therapeutic use. Comprehensive toxicological studies are needed.
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| References | |
| Additional Infomation |
TC11 is a phenylphthalimide derivative that induces apoptosis by degrading MCL1 in multiple myeloma cells. It activates caspase-9 and CDK1 and has shown in vivo activity against multiple myeloma xenografts. The compound is used as a research tool for studying MCL1 biology and is not currently in clinical trials.
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| Molecular Formula |
C20H22N2O2
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|---|---|
| Molecular Weight |
322.40
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| Exact Mass |
322.168
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| CAS # |
100823-03-8
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| PubChem CID |
1235479
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| Appearance |
White to yellow solid powder
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| LogP |
4.962
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
486
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NRPIRIUWEKTNGQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H22N2O2/c1-11(2)14-6-5-7-15(12(3)4)18(14)22-19(23)16-9-8-13(21)10-17(16)20(22)24/h5-12H,21H2,1-4H3
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| Chemical Name |
5-amino-2-[2,6-di(propan-2-yl)phenyl]isoindole-1,3-dione
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (155.09 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.75 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1017 mL | 15.5087 mL | 31.0174 mL | |
| 5 mM | 0.6203 mL | 3.1017 mL | 6.2035 mL | |
| 10 mM | 0.3102 mL | 1.5509 mL | 3.1017 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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