| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
GSK1379725A (AU1) is the first small molecule selective for BPTF over Brd4, as an inhibitor of Brd4 and a selective BPTF ligand with Kd of 2.8 μM. AU1 is active in a cell-based reporter assay. No binding is detected with Brd4. Three new Brd4 inhibitors with submicromolar affinity were also discovered. Brd4 hits were validated in a thermal stability assay and potency determined via fluorescence anisotropy. The speed, ease of interpretation, and low protein concentration needed for protein-observed (19)F NMR experiments in a multiprotein format offers a new method to discover and characterize selective ligands for bromodomain-containing proteins.
| ln Vitro |
There is an upper limit on the chemical exchange rate based on the separation of the bound and unbound resonances (171 Hz) from the NMR titration of GSK1379725A. The upper limit of Kd, if a series of protein-small molecule interactions (e.g., chymotrypsin: proflavin k1=1.2×108 M-1 s-1) have a correlation rate of 1×108 M-1 s-1 as their upper limit, follows. An estimate of 8 μM was made based on this experiment. By using unlabeled BPTF as a supplementary direct binding assay, ITC was utilized to assess non-fluorinated proteins with greater accuracy. The intermediate exchange resonance broadening we discovered by PrOF NMR is consistent with the Kd of 2.8 μM that we measured. A full selectivity panel against other bromodomains is still required, even though GSK1379725A has been demonstrated to be selective against Brd4. Of the five cell assays with an EC50 of 500 nM, only GSK1379725A was shown to be active using a ChEMBL database search. Furthermore, the kinase activity of GSK1379725A has not been documented, despite the growing popularity of PKIS libraries for screening [1].
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| References |
| Molecular Formula |
C23H23FN6O3
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|---|---|
| Molecular Weight |
450.465527772903
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| Exact Mass |
450.181
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| CAS # |
1802251-00-8
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| Related CAS # |
(S)-GSK1379725A;2359618-49-6
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| PubChem CID |
44525934
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
662
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C=CC(=CC=1)NC1=NC=CC(=N1)N1CCC(C1)NC(NC1C=CC=C(C(=O)OC)C=1)=O
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| InChi Key |
LLVPDBRSUHNJQQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H23FN6O3/c1-33-21(31)15-3-2-4-18(13-15)27-23(32)28-19-10-12-30(14-19)20-9-11-25-22(29-20)26-17-7-5-16(24)6-8-17/h2-9,11,13,19H,10,12,14H2,1H3,(H,25,26,29)(H2,27,28,32)
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| Chemical Name |
3-(3-{1-[2-(4-Fluoro-phenylamino)-pyrimidin-4-yl]-pyrrolidin-3-yl}-ureido)-benzoic acid methyl ester
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| Synonyms |
AU1; AU-1; AU 1; GSK1379725A; GSK 1379725 A; GSK-1379725-A;
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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 (~221.99 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.55 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 (5.55 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2199 mL | 11.0995 mL | 22.1990 mL | |
| 5 mM | 0.4440 mL | 2.2199 mL | 4.4398 mL | |
| 10 mM | 0.2220 mL | 1.1100 mL | 2.2199 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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