| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
BRPF1 bromodomain (pIC50 = 6.0); BRPF2 bromodomain (pIC50 = 4.3)
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| ln Vitro |
GSK6853 exhibits characteristics appropriate for cellular and in vivo investigations. It is a highly selective, soluble, cell active (20 nM), and potent (300 pM) inhibitor of the BRPF1 bromodomain. GSK6853 is an analogue of GSK6853 that is less active and has an alkylated 5-amide[1].
GSK9311 inhibits BRPF bromodomain with pIC50 values of 6.0 and 4.3 for BRPF1 and BRPF2, respectively. It exhibits 125- and 185-fold reduced potency compared to its structural analog GSK6853 in cell-free and cell-based assays. GSK9311 is a less active analog in which the 5-amide is alkylated, resulting in significantly diminished BRPF1 binding affinity. The compound is used as a negative control in epigenetic research to validate the selectivity and specificity of BRPF-targeting probes. |
| ln Vivo |
In male CD1 mouse, following IV administration (1 mg/kg), GSK6853 demonstrates a high blood clearance of 107 mL/min/kg, a moderate volume of distribution (5.5 L/kg) and a moderate terminal half-life of 1.7 h. Oral administration (PO, 3 mg/kg) achieves a moderate systemic exposure, with a Cmax of 42 ng/mL and Tmax of 1.5 h, resulting in a bioavailability of 22%. The intraperitoneal route of administration (IP, 3 mg/kg) reaches a Cmax of 469 ng/mL and Tmax of 0.25 h, resulting in a bioavailability of 85%. The results indicate that the IP route of administration would be suitable for dosing this molecule in potential PKPD models.
In vivo data for GSK9311 are limited as the compound is primarily used as a negative control in cellular and biochemical assays rather than for in vivo efficacy studies. The compound is not intended for therapeutic applications but serves as a tool to confirm the on-target effects of BRPF inhibitors in experimental settings. |
| Enzyme Assay |
BRPF bromodomain binding affinity is measured using time-resolved fluorescence resonance energy transfer (TR-FRET) or AlphaScreen assays with recombinant BRPF1 and BRPF2 bromodomains. pIC50 values are determined from dose-response curves. Selectivity profiling is conducted against other bromodomain-containing proteins to confirm the specificity of the parent compound GSK6853.
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| Cell Assay |
Cellular activity is assessed in cell-based assays measuring BRPF1-dependent transcriptional activity or BRPF1 target gene expression. GSK9311 is used as a negative control at concentrations up to 20 nM to demonstrate that observed cellular effects are specifically due to BRPF1 inhibition rather than off-target effects. The compound's reduced potency compared to GSK6853 confirms its utility as a negative control.
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| Animal Protocol |
1 mg/kg; i.p. or i.v. injection
CD1 mice Animal studies for GSK9311 are not typically performed as the compound serves as a negative control rather than an active therapeutic agent. In vivo studies of the parent compound GSK6853 demonstrate properties suitable for cellular and in vivo studies, but GSK9311 itself is not used for efficacy evaluation in animal models. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for GSK9311 are limited as the compound is not intended for therapeutic development. The parent compound GSK6853 demonstrates properties suitable for cellular and in vivo studies with good solubility and cell activity. GSK9311 is used primarily as a research tool rather than for pharmacokinetic characterization.
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| Toxicity/Toxicokinetics |
Toxicological data for GSK9311 are limited as the compound is used for research purposes only and not for therapeutic development. Standard laboratory safety precautions should be observed during handling. The compound is not intended for human use and has not been evaluated in formal toxicology studies.
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| References | |
| Additional Infomation |
GSK9311 is a negative control for the SGC epigenetic probe GSK6853, which is a potent (300 pM), soluble, cell-active (20 nM), and highly selective inhibitor of the BRPF1 bromodomain. GSK9311 is used to confirm that biological effects observed with GSK6853 are specifically due to BRPF1 inhibition. The compound is valuable for validating selectivity and specificity in epigenetic research.
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| Molecular Formula |
C24H31N5O3
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|---|---|---|
| Molecular Weight |
437.534645318985
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| Exact Mass |
437.242
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| CAS # |
1923851-49-3
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| Related CAS # |
GSK9311 hydrochloride;2253733-09-2
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| PubChem CID |
121232406
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| Appearance |
White to off-white solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
691
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@H]1CNCCN1C2=C(N(CC)C(C3=CC=CC=C3OC)=O)C=C(C(N4C)=C2)N(C)C4=O
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| InChi Key |
WFXIHQFRQPGCCR-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C24H31N5O3/c1-6-28(23(30)17-9-7-8-10-22(17)32-5)20-13-18-19(27(4)24(31)26(18)3)14-21(20)29-12-11-25-15-16(29)2/h7-10,13-14,16,25H,6,11-12,15H2,1-5H3/t16-/m1/s1
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| Chemical Name |
N-[1,3-dimethyl-6-[(2R)-2-methylpiperazin-1-yl]-2-oxobenzimidazol-5-yl]-N-ethyl-2-methoxybenzamide
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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 (5.71 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 (5.71 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.71 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 | 2.2856 mL | 11.4278 mL | 22.8556 mL | |
| 5 mM | 0.4571 mL | 2.2856 mL | 4.5711 mL | |
| 10 mM | 0.2286 mL | 1.1428 mL | 2.2856 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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 X-ray structure of BRPF1 with1(PDB 4UYE).ACS Med Chem Lett.2016 May 9;7(6):552-7. |
 Potency for endogenous cellular BRPF1. pIC50of34for BRPF1 and BRD3 measured in a chemoproteomic competition binding assay.ACS Med Chem Lett.2016 May 9;7(6):552- |
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