GSK4028 is the enantiomeric isomer and a negative control of GSK4027, which is a PCAF/GCN5 bromodomain chemical probe, the pIC50 of GSK4028 is 4.9 in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. p300/CREB binding protein associated factor (PCAF/KAT2B) and general control nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways, and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. The probe was optimized from a weakly potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomain, high solubility, cellular target engagement, and ≥18000-fold selectivity over the BET family, together with ≥70-fold selectivity over the wider bromodomain families.
Physicochemical Properties
| Molecular Formula | C17H21BRN4O |
| Molecular Weight | 377.278842687607 |
| Exact Mass | 376.089 |
| CAS # | 2079886-19-2 |
| Related CAS # | GSK 4027;2079896-25-4 |
| PubChem CID | 132941768 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 2.5 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 23 |
| Complexity | 513 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | BrC1C(N(C)N=CC=1N[C@@H]1CN(C)C[C@H](C2C=CC=CC=2)C1)=O |
| InChi Key | VZAFGXCWAWRULT-KGLIPLIRSA-N |
| InChi Code | InChI=1S/C17H21BrN4O/c1-21-10-13(12-6-4-3-5-7-12)8-14(11-21)20-15-9-19-22(2)17(23)16(15)18/h3-7,9,13-14,20H,8,10-11H2,1-2H3/t13-,14+/m1/s1 |
| Chemical Name | 4-bromo-2-methyl-5-[[(3S,5S)-1-methyl-5-phenylpiperidin-3-yl]amino]pyridazin-3-one |
| Synonyms | GSK4028; GSK-4028; GSK 4028 |
| 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) |
Biological Activity
| ln Vitro | The enantiomeric negative control of PCAF/GCN5 bromodomain chemical probe GSK4027 is GSK4028. GSK4028's pIC50 is 4.9. In the TR-FRET test, GSK4028 also showed efficacy against BRD4 BD1 and BRD9, with pIC50 <4.3 and 4.5±0.13, respectively [1]. |
| References |
[1]. Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe. J Med Chem. 2017 Jan 26;60(2):695-709. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~265.06 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.63 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 (6.63 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.63 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 | 2.6506 mL | 13.2528 mL | 26.5055 mL | |
| 5 mM | 0.5301 mL | 2.6506 mL | 5.3011 mL | |
| 10 mM | 0.2651 mL | 1.3253 mL | 2.6506 mL |