| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
CK1α
Casein kinase 1alpha (CK1alpha). TMX-4116 is a targeted protein degrader that induces E3 ubiquitin ligase-mediated degradation of CK1alpha. It selectively degrades CK1alpha over PDE6D, IKZF1, and IKZF3. |
|---|---|
| ln Vitro |
In MOLT4 cells, TMX-4116 (Compound 16; 1 μM; 4 hours) exhibits a strong predilection for CK1α breakdown [1]. Without downregulating PDE6D, IKZF1, or IKZF3, TMX-4116 (250 nM, 4 hours) causes primary targeted degradation of CK1α in MOLT4 cells [1]. TMX-4116
TMX-4116 induces degradation of CK1alpha in MOLT4, Jurkat, and MM.1S cells with DC₅0 < 200 nM. It selectively degrades CK1alpha over PDE6D, IKZF1, and IKZF3 at concentrations ranging from 0.04 to 1 microM. |
| ln Vivo |
No in vivo activity data has been reported for TMX-4116 in available literature. As a targeted protein degrader, it has potential for studying CK1alpha biology and as a therapeutic strategy for multiple myeloma.
|
| Enzyme Assay |
Targeted protein degradation assays: TMX-4116 is incubated with CK1alpha protein and E3 ubiquitin ligase components. Degradation of CK1alpha is measured by Western blot. Ternary complex formation is assessed using biophysical methods (e.g., SPR or ITC).
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: MOLT4 cells Tested Concentrations: 1 μM Incubation Duration: 4 hrs (hours) Experimental Results: demonstrated a high degradation preference for CK1α. Western Blot Analysis[1] Cell Types: MOLT4, Jurkat, and MM.1S cells Tested Concentrations: 0 nM, 40 nM, 200 nM, 1 μM Incubation Duration: 4 hrs (hours) Experimental Results: demonstrated a high degradation preference for CK1α with the DC50 value less than 200 nM in MOLT4, Jurkat, and MM.1S cells. Cells (MOLT4, Jurkat, MM.1S) are treated with TMX-4116. CK1alpha protein levels are measured by Western blot at various time points and concentrations. DC₅0 values are calculated from dose-response curves. Selectivity is assessed by measuring levels of other proteins (PDE6D, IKZF1, IKZF3). |
| Animal Protocol |
Animal models of multiple myeloma could be used to evaluate TMX-4116 in vivo. Efficacy would be assessed by tumor growth inhibition and survival. Pharmacodynamic markers (CK1alpha degradation) would be measured in tumor tissues.
|
| ADME/Pharmacokinetics |
TMX-4116 has a molecular weight of 389.43 and a molecular formula of C1₇H1₉N₅O4S. It is a CK1alpha degrader. Detailed pharmacokinetic parameters have not been reported.
|
| Toxicity/Toxicokinetics |
No toxicity data has been published for TMX-4116. As a research compound, it is not intended for human therapeutic use. Its selectivity for CK1alpha over other proteins suggests a potential for reduced off-target toxicity.
|
| References | |
| Additional Infomation |
TMX-4116 is a casein kinase 1alpha (CK1alpha) degrader. It induces selective degradation of CK1alpha with DC₅0 < 200 nM in MOLT4, Jurkat, and MM.1S cells. It is used in multiple myeloma and protein degradation research. The compound is for research use only and has not entered clinical trials.
|
| Molecular Formula |
C17H19N5O4S
|
|---|---|
| Molecular Weight |
389.428861856461
|
| Exact Mass |
389.115
|
| CAS # |
2766385-56-0
|
| PubChem CID |
162641722
|
| Appearance |
Off-white to gray solid powder
|
| LogP |
0.6
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
27
|
| Complexity |
614
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N1C(=O)CCC(N2C=C(C3C(OC)=C(C(N4CCCC4)=O)SC=3)N=N2)C1=O
|
| InChi Key |
OOIINFBRWZQRRM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H19N5O4S/c1-26-14-10(9-27-15(14)17(25)21-6-2-3-7-21)11-8-22(20-19-11)12-4-5-13(23)18-16(12)24/h8-9,12H,2-7H2,1H3,(H,18,23,24)
|
| Chemical Name |
3-[4-[4-methoxy-5-(pyrrolidine-1-carbonyl)thiophen-3-yl]triazol-1-yl]piperidine-2,6-dione
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 100 mg/mL (256.79 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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: ≥ 2.5 mg/mL (6.42 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5679 mL | 12.8393 mL | 25.6786 mL | |
| 5 mM | 0.5136 mL | 2.5679 mL | 5.1357 mL | |
| 10 mM | 0.2568 mL | 1.2839 mL | 2.5679 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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