| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
SJ6986 targets G1 to S phase transition 1/2 (GSPT1/2), small GTPases involved in translation termination and cell cycle progression. It is a CRBN modulator that specifically induces the degradation of GSPT1/2 via the ubiquitin-proteasome pathway. SJ6986 exhibits a DC50 of 2.1 nM with a Dmax of 99% for GSPT1.
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| ln Vitro |
In the MV4-11, MHH-CALL-4, MB002, MB004, and HD-MB03 cell lines, the EC50 values of SJ6986 are 1.5 nM, 0.4 nM, 726 nM, 336 nM, and 3583 nM, respectively [1].
In vitro, SJ6986 demonstrates potent anti-proliferative activity against various acute lymphoblastic leukemia cell lines, with EC50 values of 1.5 nM in MV4-11 cells, 0.4 nM in MHH-CALL-4 cells, 726 nM in MB002 cells, 336 nM in MB004 cells, and 3583 nM in HD-MB03 cells. In MV4-11 cell proliferation assays with a 3-day incubation, the EC50 is 1.5 nM. Western blot analysis shows that GSPT1 protein levels decrease in a dose- and time-dependent manner following treatment with SJ6986 (0-10 μM; 4 and 24 hours) in MV4-11 cells. |
| ln Vivo |
The t1/2 of SJ6986 in CD1 mice was 3.44 hours at 3 mg/kg intravenously, and the tmax was 0.25 hours at 10 mg/kg oral (%F = 84) [1].
In vivo, SJ6986 demonstrates oral bioavailability and efficacy against acute lymphoblastic leukemia xenografts. In CD1 mice, intravenous administration at 3 mg/kg yields a half-life (t1/2) of 3.44 hours, while oral administration at 10 mg/kg achieves a Tmax of 0.25 hours and an oral bioavailability of 84% (%F=84). |
| Enzyme Assay |
The in vitro enzyme/receptor binding assay for SJ6986 typically involves assessing its binding to cereblon (CRBN) and its ability to induce GSPT1/2 ubiquitination. CRBN binding affinity can be measured using surface plasmon resonance or fluorescence polarization assays with recombinant CRBN protein. The degradation of GSPT1/2 is evaluated in cell-free systems using ubiquitination assays with purified E1, E2, and E3 ligase components, followed by immunoblotting for polyubiquitinated GSPT1. DC50 values are determined by quantifying remaining GSPT1 protein levels via ELISA or Western blot following incubation with the compound.
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| Cell Assay |
Cell proliferation assay [1]
Cell Types: MV4-11 cells. Tested Concentrations: 0-100 μM. Incubation Duration: 3 days. Experimental Results: EC50 is 1.5 nM. Western Blot Analysis[1] Cell Types: MV4-11 cells. Tested Concentrations: 0-10μM. Incubation Duration: 4 hrs (hours) and 24 hrs (hours). Experimental Results: GSPT1 protein levels diminished in a dose- and time-dependent manner. The in vitro cell-based assay for SJ6986 involves culturing acute lymphoblastic leukemia cell lines, such as MV4-11 or MHH-CALL-4. Cells are seeded in multi-well plates and treated with SJ6986 at various concentrations (typically 0-100 μM) for 3 days. Cell viability is assessed using CellTiter-Glo or MTT assays to determine EC50 values. For mechanistic studies, cells are treated with SJ6986 (0-10 μM) for 4 or 24 hours, and GSPT1 protein levels are analyzed by Western blot to confirm target degradation. CRBN engagement can be verified using a CRBN binding assay. |
| Animal Protocol |
In vivo animal studies for SJ6986 are conducted in mouse xenograft models of acute lymphoblastic leukemia. Tumor-bearing mice are administered SJ6986 orally or intravenously at various doses (e.g., 3 mg/kg IV, 10 mg/kg PO). Tumor volume is measured over time to assess efficacy. For pharmacokinetic studies, blood samples are collected at multiple time points following administration, and plasma concentrations of SJ6986 are analyzed by LC-MS/MS. Tissues may also be collected for analysis of GSPT1 degradation by Western blot.
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| ADME/Pharmacokinetics |
SJ6986 exhibits favorable pharmacokinetic properties with oral bioavailability. In CD1 mice, intravenous administration at 3 mg/kg shows a half-life of 3.44 hours. Oral administration at 10 mg/kg reaches peak plasma concentration at 0.25 hours (Tmax) with an oral bioavailability of 84%. The compound is soluble in DMSO (55 mg/mL) and can be formulated for in vivo administration using vehicles such as 10% DMSO + 90% saline.
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| Toxicity/Toxicokinetics |
The toxicity profile of SJ6986 has been evaluated in preclinical studies. As a GSPT1/2 degrader, its primary on-target effects relate to disruption of translation termination and cell cycle progression. No significant off-target toxicity has been reported, consistent with its high selectivity for GSPT1/2 over other proteins, including IKZF1 and IKZF3. Standard toxicology assessments would include acute and sub-chronic toxicity studies in rodents, with endpoints including clinical signs, body weight, clinical pathology, and histopathology. The compound is for research use only.
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| References | |
| Additional Infomation |
SJ6986 is a research compound and has not been approved for clinical use. It is a CRBN modulator and molecular glue degrader that specifically targets GSPT1/2 for degradation via the ubiquitin-proteasome pathway. The compound displays selectivity for GSPT1/2 over more than 9,000 other proteins. SJ6986 has demonstrated efficacy against acute lymphoblastic leukemia cell lines and xenografts, making it a valuable tool for cancer research. It is available only for research purposes.
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| Molecular Formula |
C20H14F3N3O7S
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|---|---|
| Molecular Weight |
497.40
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| Exact Mass |
497.05
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| Elemental Analysis |
C, 48.30; H, 2.84; F, 11.46; N, 8.45; O, 22.52; S, 6.45
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| CAS # |
2765625-93-0
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| PubChem CID |
155925914
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| Appearance |
White to yellow solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
981
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C=C(C=C3)NS(=O)(=O)C4=CC=CC=C4OC(F)(F)F
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| InChi Key |
RKAFYSIKAVFVPS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H14F3N3O7S/c21-20(22,23)33-14-3-1-2-4-15(14)34(31,32)25-10-5-6-11-12(9-10)19(30)26(18(11)29)13-7-8-16(27)24-17(13)28/h1-6,9,13,25H,7-8H2,(H,24,27,28)
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| Chemical Name |
N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-2-(trifluoromethoxy)benzenesulfonamide
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| Synonyms |
SJ6986; SJ-6986; SJ 6986;
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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 (~201.05 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.03 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 25.0 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 | 2.0105 mL | 10.0523 mL | 20.1045 mL | |
| 5 mM | 0.4021 mL | 2.0105 mL | 4.0209 mL | |
| 10 mM | 0.2010 mL | 1.0052 mL | 2.0105 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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