| Size | Price | Stock | Qty |
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| 1mg |
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| 10mg |
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| Targets |
PDE6D
TMX-4100 targets phosphodiesterase 6D (PDE6D), a prenyl-binding protein that plays a critical role in the trafficking of prenylated proteins to cellular membranes. PDE6D is involved in the localization and function of Ras and Ras-related proteins, which are important in cancer cell signaling. TMX-4100 is a molecular glue degrader that promotes the interaction between PDE6D and the E3 ubiquitin ligase cereblon. This interaction induces ubiquitination of PDE6D and its subsequent degradation by the proteasome. By degrading PDE6D, TMX-4100 disrupts the trafficking of prenylated proteins and impairs cancer cell signaling. |
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| ln Vitro |
In MOLT4 cells, compound 3 (TMX-4100; 1 μM; 4 h) shows a strong predilection for PDE6D degradation [1]. In MOLT4 cells, TMX-4100 showed superior proteome-wide degradation selectivity when compared to the PDE6D degrader FPFT-2216 [1]. KRAS-dependent cell lines (MIA PaCa-2, NCI-H358, AGS, and PA-TU-8988T cells) are not inhibited by TMX-4100 [1].
TMX-4100 demonstrates potent in vitro degradation of PDE6D. In MOLT4, Jurkat, and MM.1S tumor cells, TMX-4100 exhibits high degradation preference with DC50 values less than 200 nM. The compound is a molecular glue degrader that promotes the interaction between PDE6D and cereblon, inducing ubiquitination and degradation of PDE6D. These in vitro findings confirm the compound's potent and selective degradation of PDE6D in cancer cell lines. TMX-4100's mechanism of action as a degrader differs from traditional enzyme inhibitors. |
| ln Vivo |
In vivo activity data for TMX-4100 are not extensively documented. The compound is used in multiple myeloma research, suggesting potential in vivo efficacy in animal models of multiple myeloma. Standard in vivo efficacy studies would involve mouse xenograft models of multiple myeloma, where TMX-4100 would be administered via oral or parenteral routes. Tumor growth and PDE6D protein levels in tumors would be assessed. Further studies are needed to fully characterize the compound's in vivo activity and therapeutic potential.
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| Enzyme Assay |
The in vitro degradation assay for TMX-4100 involves measuring its ability to induce degradation of PDE6D in cells. Cells (MOLT4, Jurkat, MM.1S) are treated with TMX-4100 at various concentrations for a defined period. PDE6D protein levels are measured by Western blot or ELISA. The DC50 value (concentration for 50% degradation) is determined by fitting the degradation data to a dose-response curve. Additionally, the interaction between PDE6D and cereblon can be assessed by co-immunoprecipitation. These assays confirm the compound's degradation activity.
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| 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 PDE6D. 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 PDE6D with the DC50 value less than 200 nM. In vitro cellular assays for TMX-4100 typically use cancer cell lines such as MOLT4, Jurkat, and MM.1S. Cells are treated with TMX-4100 at various concentrations. PDE6D protein levels are measured by Western blot to assess degradation. Cell viability and proliferation are measured using standard assays such as MTT or CellTiter-Glo to assess the functional consequences of PDE6D degradation. The compound's effects on cancer cell signaling pathways can be assessed by Western blot for downstream targets. These assays confirm the compound's cellular activity. |
| Animal Protocol |
In vivo animal experiments for TMX-4100 would typically use mouse xenograft models of multiple myeloma. As a PDE6D degrader, TMX-4100 would be administered via oral or parenteral routes. Tumor growth would be monitored. Tumor tissues would be collected for analysis of PDE6D protein levels and biomarkers of cell proliferation and apoptosis. Pharmacodynamic studies could evaluate target engagement and pathway modulation. The compound's potential for treating multiple myeloma supports the use of appropriate animal models.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of TMX-4100 are not extensively documented. As a small-molecule degrader, the compound's molecular weight and chemical properties would influence its absorption, distribution, metabolism, and excretion (ADME). The compound's ability to induce degradation of PDE6D suggests that it can reach intracellular targets. Further pharmacokinetic studies are necessary to fully characterize its PK profile and support its development as a therapeutic agent for multiple myeloma.
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| Toxicity/Toxicokinetics |
Toxicological data for TMX-4100 are not extensively available in the public domain. As a research compound used for cancer studies, TMX-4100 has not undergone extensive toxicological evaluation. Standard cytotoxicity assays in cancer cell lines are typically performed to assess antiproliferative effects. In animal studies, tolerability and potential adverse effects would be monitored. As a molecular glue degrader, the compound's off-target degradation effects would need to be carefully evaluated. Further preclinical toxicology studies would be required before clinical development.
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| References | |
| Additional Infomation |
TMX-4100 is a selective PDE6D degrader with DC50 values less than 200 nM in MOLT4, Jurkat, and MM.1S cells. It is a molecular glue degrader that promotes PDE6D-cereblon interaction, inducing ubiquitination and degradation of PDE6D. The compound is used in multiple myeloma research. No clinical trials or regulatory approvals have been reported. TMX-4100 is available as a research-grade compound.
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| Molecular Formula |
C11H10N4O2S
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|---|---|
| Molecular Weight |
262.29
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| Exact Mass |
262.052
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| CAS # |
2367619-63-2
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| PubChem CID |
151449452
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| Appearance |
White to off-white solid powder
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| LogP |
0.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
365
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C(=O)CCC(N2C=C(C3C=CSC=3)N=N2)C1=O
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| InChi Key |
PGEUBQZQGXWTFO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H10N4O2S/c16-10-2-1-9(11(17)12-10)15-5-8(13-14-15)7-3-4-18-6-7/h3-6,9H,1-2H2,(H,12,16,17)
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| Chemical Name |
3-(4-thiophen-3-yltriazol-1-yl)piperidine-2,6-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 |
| 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: 100 mg/mL (381.26 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.71 mg/mL (2.71 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 7.1 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: ≥ 0.71 mg/mL (2.71 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 7.1 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8126 mL | 19.0629 mL | 38.1257 mL | |
| 5 mM | 0.7625 mL | 3.8126 mL | 7.6251 mL | |
| 10 mM | 0.3813 mL | 1.9063 mL | 3.8126 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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