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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
SF2523 (SF-2523; SF 2523) is a novel, selective and potent dual inhibitor of PI3K-BRD4 with potential anticancer activities. Its respective IC50 values for PI3K, PI3K, DNA-PK, BRD4, and mTOR are 34 nM, 158 nM, 9 nM, 241 nM, and 280 nM. BRD4 cannot bind to the MYCN promoter PS1/PS2 because of SF2523. It inhibits the M1-M2 transition and lowers p-AKT and N-MYC levels in a number of neuroblastoma cell lines. MYCN and Cyclin D1, the MYCN target, have lower protein levels after being treated with SF2523. It also prevents AKT activation by preventing Ser473-phosphorylation of AKT. In vitro and in vivo PI3K/BRD4 signaling is compromised by the dual-action inhibitor SF2523, which also provides the greatest MYC down-regulation. The simultaneous inhibition of PI3K and BRD4 prevents MYC expression and activation, encourages MYC degradation, and significantly reduces the growth and metastasis of cancer cells. The combination of these results points to the dual-activity inhibitor as a very promising lead compound for the creation of brand-new anticancer therapeutics.
| Targets |
PI3Kα (IC50 = 34 nM); PI3Kγ (IC50 = 158 nM); BRD4 (BD1) (IC50 = 241 nM); DNA-PK (IC50 = 9 nM); mTOR (IC50 = 280 nM)
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| ln Vitro |
SF2523 blocks BRD4 binding to MYCN promoter PS1/PS2. It inhibits the M1-M2 transition and lowers p-AKT and N-MYC levels in a number of neuroblastoma cell lines. Treatment with SF2523 lowers the protein levels of MYCN and Cyclin D1, the MYCN target, and prevents AKT activation by preventing AKT's Ser473 phosphorylation. SF2523 interacts strongly with BRD4 in its entirety (Kd = 140 nM) and similarly with its first BD (BD1) (Kd = 150 nM), but it binds to BRD4's second BD (BD2) less strongly (Kd = 710 nM). According to a comparison of SF2523's binding affinities for other proteins' BDs, it binds to BDs of BRD4, BRD2, and BRD3 equally well, moderately to BDs of CECR2 and BRDT, but much weaker to other BDs[3].
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| ln Vivo |
SF2523 blocks spontaneous metastasis and tumor growth. SF2523 has demonstrated animal efficacy results without toxicity in the following 4 animal models: orthotopic pancreatic model, multiple myeloma model, renal cell carcinoma model, neuroblastoma xenograft model[2]. In vivo, SF2523 targets PI3K- and BRD4-driven oncogenic pathways. In contrast to a combination of an equipotent PI3K inhibitor and a BRD4 inhibitor, SF2523 is less toxic to the host organism in vivo[3].
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| Enzyme Assay |
SF2523 is a novel, selective and potent dual inhibitor of PI3K-BRD4 with IC50s of 34 nM, 158 nM, 9 nM, 241 nM and 280 nM for PI3Kα, PI3Kγ, DNA-PK, BRD4 and mTOR, respectively.
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| Cell Assay |
SKNBE2 cells are serum-starved for 4 h, stimulated with 50 ng/mL IGF, and treated with 1 μM JQ1, 5 μM SF2523, 10 μM SF1126, 1 μM BKM120, 1 μM BEZ235, or 200 nM CAL101 for 24 h. RT-PCR is then carried out after total RNA has been extracted from the harvested cells.
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| Animal Protocol |
Nude mice (8-wk old, female, NSG) with xenografted tumor
50 mg/kg i.p. |
| References |
| Molecular Formula |
C19H17NO5S
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| Molecular Weight |
371.41
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| Exact Mass |
371.0827
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| Elemental Analysis |
C, 61.44; H, 4.61; N, 3.77; O, 21.54; S, 8.63
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| CAS # |
1174428-47-7
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| Related CAS # |
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| Appearance |
Red solid powder
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| SMILES |
C1COCCN1C2=CC(=O)C3=C(O2)C(=CS3)C4=CC5=C(C=C4)OCCO
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| InChi Key |
BYTKNUOMWLJVNQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17NO5S/c21-14-10-17(20-3-5-22-6-4-20)25-18-13(11-26-19(14)18)12-1-2-15-16(9-12)24-8-7-23-15/h1-2,9-11H,3-8H2
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| Chemical Name |
3-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-morpholin-4-ylthieno[3,2-b]pyran-7-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.73 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 (6.73 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 | 2.6924 mL | 13.4622 mL | 26.9244 mL | |
| 5 mM | 0.5385 mL | 2.6924 mL | 5.3849 mL | |
| 10 mM | 0.2692 mL | 1.3462 mL | 2.6924 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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PI3K-specific inhibitor targets BRD4.Proc Natl Acad Sci U S A. 2017 Feb 14; 114(7): E1072–E1080. |
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Morpholinothienopyrane is an inhibitor of BDs.Proc Natl Acad Sci U S A. 2017 Feb 14; 114(7): E1072–E1080. |
SF2523 blocks tumor growth.Proc Natl Acad Sci U S A. 2017 Feb 14; 114(7): E1072–E1080. |
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