| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
SJ3149 targets the casein kinase 1 alpha (CK1α) protein for degradation. CK1α is a serine/threonine kinase that is a member of the casein kinase 1 family. It plays a critical role in various cellular processes, including Wnt signaling, circadian rhythm regulation, cell cycle progression, and DNA damage response. SJ3149 is a PROTAC molecule that binds to CK1α and recruits an E3 ubiquitin ligase (cereblon, CRBN), leading to the ubiquitination and subsequent proteasomal degradation of CK1α. The compound's structure, co-crystallized with CK1α, CRBN, and DDB1, provides a rationale for its improved degradation properties. This targeted degradation approach leads to selective removal of CK1α.
|
|---|---|
| ln Vitro |
In vitro, SJ3149 is a highly potent and selective degrader of CK1α. It has a DC50 of 3.7 nM and achieves a Dmax of 95% degradation in MOLM-13 cells, indicating near-complete depletion of the target protein. The compound potently inhibits the viability of MOLM-13 cells with an IC50 of 13 nM. In a panel of 115 cancer cell lines, SJ3149 displays a broad antiproliferative activity profile. The compound's degradation activity is selective for CK1α, preserving other proteins. SJ3149 also co-degrades multiple SACK1(A-H) proteins. The compound's in vitro activity is characterized by its potent degradation and antiproliferative effects.
|
| ln Vivo |
In vivo, SJ3149 is a selective and potent degrader of CK1α protein. It has anti-tumor activity in vivo. However, specific animal model studies, dosing regimens, and quantitative outcomes such as tumor growth inhibition have not been extensively reported in the available literature. The compound's in vivo efficacy is supported by its potent in vitro degradation and antiproliferative activity. Further in vivo studies would be required to fully characterize its efficacy, safety, and pharmacokinetic properties.
|
| Enzyme Assay |
In vitro enzyme or receptor binding assay protocols are not directly applicable to SJ3149, as it is a protein degrader rather than a traditional enzyme inhibitor. Its activity is assessed by measuring the degradation of its target protein, CK1α. A standard protocol involves treating cells with varying concentrations of SJ3149 for a defined period (e.g., 4-24 hours). The levels of CK1α protein are then measured by Western blot analysis using anti-CK1α antibodies. The concentration required for 50% degradation (DC50) and the maximum degradation (Dmax) are determined from the dose-response curve.
|
| Cell Assay |
In vitro cell-based assay protocols for SJ3149 involve treating cancer cell lines with the compound to assess its effects on cell viability and protein degradation. A standard protocol would involve seeding cells (e.g., MOLM-13) in multi-well plates and treating them with varying concentrations of SJ3149 for 72 hours. Cell viability is measured using CellTiter-Glo or MTT assays to determine the IC50. For degradation studies, cells are treated with the compound for 4-24 hours, and CK1α protein levels are assessed by Western blot. Appropriate controls include vehicle-treated cells.
|
| Animal Protocol |
In vivo animal experimental protocols for SJ3149 have not been extensively reported. Based on its mechanism as a CK1α degrader with anti-tumor activity, potential studies might involve using mouse xenograft models. A hypothetical protocol would involve implanting cancer cells (e.g., MOLM-13) subcutaneously in immunodeficient mice, allowing tumors to reach a certain size, and then administering SJ3149 via oral gavage or intraperitoneal injection at doses determined from preliminary pharmacokinetic and tolerability studies. Endpoints would include tumor volume measurement, tumor weight, and assessment of CK1α degradation in tumor tissues by Western blot.
|
| References | |
| Additional Infomation |
SJ3149 is a research-grade compound that functions as a selective and potent CK1α protein degrader with anti-tumor activity. It has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action involves targeted degradation of CK1α via the ubiquitin-proteasome pathway. The compound is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
|
| CAS # |
3026986-17-1
|
|---|---|
| Appearance |
White to light yellow solid powder
|
| Density |
1.497±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)
|
| Boiling Point |
722.6±60.0 °C(predicted)
|
| LogP |
0
|
| 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 :~75 mg/mL (~199.27 mM; with sonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (7.97 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 30.0 mg/mL clear DMSO stock solution and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up 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: ≥ 3 mg/mL (7.97 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 30.0 mg/mL clear DMSO stock solution and add it to 900 μL of 20% SBE-β-CD saline solution 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. (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
