| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Cereblon
ENL (Eleven-Nineteen Leukemia); CRBN (Cereblon), an E3 ubiquitin ligase. |
|---|---|
| ln Vitro |
SR-1114 elicits potent in vitro degradation of ENL. In MV4;11 cells, SR-1114 degrades ENL with a DC50 of 150 nM. In MOLM-13 cells, the DC50 is 311 nM, and in OCI/AML-2 cells, the DC50 is 1.65 microM. The degradation is rapid and dependent on cereblon (CRBN).
|
| ln Vivo |
No specific in vivo activity has been reported for SR-1114; however, as a potent ENL degrader, it is expected to have significant in vivo efficacy in xenograft models of ENL-dependent leukemias. Such studies are currently ongoing for this research compound.
|
| Enzyme Assay |
N/A; as a complete PROTAC molecule, its binding to ENL and cereblon is assessed using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to determine binding affinities. The ENL-cereblon ternary complex formation can be studied using time-resolved FRET (TR-FRET) or AlphaLISA assays.
|
| Cell Assay |
The in vitro degradation activity of SR-1114 is evaluated in ENL-expressing leukemia cell lines, including MV4;11, MOLM-13, and OCI/AML-2. Cells are treated with increasing concentrations of the compound (e.g., 1 nM to 10 uM) for a defined period, typically 4-24 hours. After treatment, cell lysates are prepared and ENL protein levels are measured by Western blotting or quantitative proteomics to determine DC50 values.
|
| Animal Protocol |
N/A; in vivo efficacy studies for SR-1114 would typically be conducted in mouse xenograft models of ENL-dependent leukemias. The compound would be formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered via oral gavage, IP, or IV injection. Tumor growth inhibition, ENL degradation in tumor tissue, and overall animal health would be monitored.
|
| ADME/Pharmacokinetics |
SR-1114 has a molecular weight of 830.9, a molecular formula of C39H42N8O11S, and a purity of >98%. It is typically stored as a solid powder at -20degC for up to 3 years, protected from light, or in a solvent at -80degC for 6 months. It is soluble in DMSO.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic or clinical use. Standard safe handling practices for laboratory chemical reagents should be followed. PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license.
|
| References | |
| Additional Infomation |
ENL is part of the super elongation complex (SEC) and is frequently mutated or overexpressed in acute leukemias, including mixed-lineage leukemia (MLL). SR-1114 represents a promising strategy for targeting ENL-driven cancers by degrading the protein rather than merely inhibiting it, potentially offering a more durable anti-cancer effect and overcoming resistance mechanisms associated with conventional inhibitors.
|
| Molecular Formula |
C39H42N8O11S
|
|---|---|
| Molecular Weight |
830.86
|
| Exact Mass |
830.269
|
| CAS # |
2769141-82-2
|
| PubChem CID |
155925846
|
| Appearance |
White to off-white solid powder
|
| Density |
1.56±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)
|
| LogP |
1.2
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
19
|
| Heavy Atom Count |
59
|
| Complexity |
1660
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC(OCC(=O)NCCOCCOCCNS(=O)(=O)NC3C=CC=C(C4N=C5C=CC(C(=O)NC6CCC6)=CN5C=4)C=3)=C12
|
| InChi Key |
WPVVPCVQEBQVLL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C39H42N8O11S/c48-33-13-11-30(37(51)44-33)47-38(52)28-8-3-9-31(35(28)39(47)53)58-23-34(49)40-14-16-56-18-19-57-17-15-41-59(54,55)45-27-7-1-4-24(20-27)29-22-46-21-25(10-12-32(46)43-29)36(50)42-26-5-2-6-26/h1,3-4,7-10,12,20-22,26,30,41,45H,2,5-6,11,13-19,23H2,(H,40,49)(H,42,50)(H,44,48,51)
|
| Chemical Name |
N-cyclobutyl-2-[3-[2-[2-[2-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]ethoxy]ethoxy]ethylsulfamoylamino]phenyl]imidazo[1,2-a]pyridine-6-carboxamide
|
| 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 (~120.4 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (3.01 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 (3.01 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 (3.01 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2036 mL | 6.0179 mL | 12.0357 mL | |
| 5 mM | 0.2407 mL | 1.2036 mL | 2.4071 mL | |
| 10 mM | 0.1204 mL | 0.6018 mL | 1.2036 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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