| 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.
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| 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.
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| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (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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