| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
PIP4K2C[1].
PIP4K2C (target protein) and the VHL E3 ubiquitin ligase complex. TMX-4153 simultaneously binds to PIP4K2C via its warhead and to VHL, leading to ubiquitination and proteasomal degradation of PIP4K2C. |
|---|---|
| ln Vitro |
In MOLT4, PIP4K2C is preferentially degraded by TMX-4153 (0.01, 0.05, 0.1, 0.5, 1 µM; 6 h)[1].
In MOLT4 cells, TMX-4153 at 0.01-1 uM for 6 hours induces selective degradation of PIP4K2C. The binding affinity (KD) to PIP4K2C is 42 nM, indicating high potency. It also inhibits the viability of PIP4K2C-dependent cell lines with low micromolar IC50. |
| ln Vivo |
In vivo activity data are not publicly available. Based on its mechanism, TMX-4153 is expected to reduce PIP4K2C protein levels in animal tissues after systemic administration, potentially affecting phosphoinositide signaling and cellular metabolism.
|
| Enzyme Assay |
A non-cell binding assay is performed using surface plasmon resonance (SPR) or fluorescence polarization. Purified recombinant PIP4K2C protein is immobilized, and TMX-4153 is flowed over at increasing concentrations (1-500 nM). The KD of 42 nM is determined by fitting binding kinetics.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: MOLT4 cells Tested Concentrations: 0.01, 0.05, 0.1, 0.5, 1 µM Incubation Duration: 6 h Experimental Results: Selectively degraded PIP4K2C with the maximal level of degradation (Dmax) value of 91% at 1 µM and half-maximal degradation concentration (DC50) value of 24 nM. MOLT4 cells (or other leukemia cell lines) are seeded in 96-well plates and treated with TMX-4153 at 0.01, 0.05, 0.1, 0.5, and 1 uM for 6 hours. Cells are lysed, and PIP4K2C protein levels are measured by Western blot with anti-PIP4K2C antibody. A dose-dependent degradation is observed. |
| Animal Protocol |
No detailed in vivo data are available. In a typical experiment, TMX-4153 would be administered to mice bearing PIP4K2C-dependent tumor xenografts by intraperitoneal injection (e.g., 10-50 mg/kg) daily for 2-3 weeks. Tumor growth inhibition and PIP4K2C knockdown in tumors would be assessed.
|
| ADME/Pharmacokinetics |
TMX-4153 is a lipophilic molecule with molecular weight 1079.74, which may limit oral bioavailability. It is typically formulated in DMSO for in vitro use; for in vivo, it would require a vehicle such as 10% DMSO + 90% PEG300 or a lipid-based formulation.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are published. As a degrader of PIP4K2C, potential on-target toxicities may include disruption of phosphoinositide metabolism in normal tissues. Off-target degradation should be evaluated by proteomics. Standard chemical safety precautions apply.
|
| References | |
| Additional Infomation |
TMX-4153 is a chemical probe for studying the biological function of PIP4K2C. Its high selectivity and potency make it valuable for target validation in lipid kinase research. It is for research use only, not for therapeutic applications. Store at -20degC as a powder.
|
| CAS # |
2867519-91-1
|
|---|---|
| Appearance |
White to off-white solid powder
|
| SMILES |
ClC1=CN=C(N=C1C2=CC=CC(C3=CC=CC=C3)=C2)NC4=CC(N(C5=O)CCC5(CC6)CCN6C(CCCCCC(N[C@H](C(N7[C@H](C(N[C@@H](C)C8=CC=C(C9=C(C)N=CS9)C=C8)=O)C[C@@H](O)C7)=O)C(C)(C)C)=O)=O)=CN=C4
|
| 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 (~92.6 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (2.32 mM) 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; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 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: 2.5 mg/mL (2.32 mM) 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 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: 2.5 mg/mL (2.32 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
