| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
BET proteins (BRD2, BRD3, BRD4) and an E3 ubiquitin ligase (likely CRBN). SJ995973 is a bivalent degrader that binds to BET proteins and recruits an E3 ligase, leading to ubiquitination and proteasomal degradation of BET proteins.
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|---|---|
| ln Vitro |
In biochemical assays, SJ995973 binds to BRD4 with high affinity. In cellular assays, it induces degradation of BRD4 with DC50 = 0.87 nM and inhibits viability of MV4-11 acute myeloid leukemia cells with IC50 = 3 pM, demonstrating extraordinary potency.
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| ln Vivo |
In vivo activity data are not publicly available. Based on its cellular potency, SJ995973 is expected to reduce BET protein levels in tumors and inhibit the growth of BET-dependent cancers in mouse xenograft models at sub-nanomolar plasma concentrations.
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| Enzyme Assay |
A non-cell ternary complex assay is performed using purified BRD4 (bromodomain) and CRBN-DDB1 complex. SJ995973 is added, and complex formation is measured by AlphaScreen or SPR. The compound promotes stable ternary complex formation, leading to efficient ubiquitination in the presence of E2 enzymes.
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| Cell Assay |
MV4-11 cells are seeded in 96-well plates and treated with SJ995973 at concentrations from 1 fM to 100 nM for 4 hours (for degradation) or 72 hours (for viability). BRD4 levels are measured by Western blot to determine DC50 (0.87 nM). Viability is measured by CellTiter-Glo to determine IC50 (3 pM).
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| Animal Protocol |
No published in vivo data. In a typical study, mice bearing MV4-11 xenografts would be treated with SJ995973 by IV or IP injection (e.g., 0.1-1 mg/kg, daily). Tumor growth inhibition and BRD4 knockdown in tumors would be assessed.
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| ADME/Pharmacokinetics |
The compound has MW 730.28. Its PK properties are not published. Due to high potency, low doses may be sufficient. The compound is soluble in DMSO (100 mg/mL). For in vivo use, formulation in a vehicle such as 10% DMSO + 90% PEG300 is common.
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| Toxicity/Toxicokinetics |
No specific toxicity data are available. On-target toxicities of BET degradation include thrombocytopenia, gastrointestinal disturbances, and myelosuppression. Off-target degradation should be evaluated by proteomics. Standard safety precautions for potent compounds apply.
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| References | |
| Additional Infomation |
SJ995973 is a highly potent and selective chemical probe for studying BET protein function. Its picomolar IC50 in AML cells demonstrates the power of PROTAC technology. It is for research use only, not for therapeutic or diagnostic applications. Store at -20degC as a powder.
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| Molecular Formula |
C37H40CLN7O5S
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|---|---|
| Molecular Weight |
730.275405883789
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| Exact Mass |
729.25
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| CAS # |
2882065-25-8
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| PubChem CID |
162641697
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
51
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| Complexity |
1280
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C=CC(=CC=1)C1C2C(C)=C(C)SC=2N2C(C)=NN=C2[C@H](CC(NCCCCCNC(COC2C=CC(=CC=2)C2C(NC(CC2)=O)=O)=O)=O)N=1
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| InChi Key |
VVRONDSUSMJAEI-XIJSCUBXSA-N
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| InChi Code |
InChI=1S/C37H40ClN7O5S/c1-21-22(2)51-37-33(21)34(25-7-11-26(38)12-8-25)41-29(35-44-43-23(3)45(35)37)19-31(47)39-17-5-4-6-18-40-32(48)20-50-27-13-9-24(10-14-27)28-15-16-30(46)42-36(28)49/h7-14,28-29H,4-6,15-20H2,1-3H3,(H,39,47)(H,40,48)(H,42,46,49)/t28?,29-/m0/s1
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| Chemical Name |
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[5-[[2-[4-(2,6-dioxopiperidin-3-yl)phenoxy]acetyl]amino]pentyl]acetamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~136.93 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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 (3.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3693 mL | 6.8467 mL | 13.6934 mL | |
| 5 mM | 0.2739 mL | 1.3693 mL | 2.7387 mL | |
| 10 mM | 0.1369 mL | 0.6847 mL | 1.3693 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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