| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
ATAD2 bromodomain and ATAD2B bromodomain (BD). GSK8814 targets these bromodomains with high selectivity, showing 500-fold selectivity for ATAD2 over BRD4 BD1.
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|---|---|
| ln Vitro |
GSK8814 binds to ATAD2 with a pKd of 8.1 by isothermal titration calorimetry and shows a pIC50 of 7.3 for ATAD2 BD and 7.7 for ATAD2B BD in TR-FRET competitive ligand binding assays. It has a pKi of 8.9 in BROMOscan. Selectivity is demonstrated by pIC50 ≤4.5 against BD1/BD2 of BRD2-4 or BRDT.
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| ln Vivo |
In intact cells, GSK8814 effectively disrupts histone H3.3 interaction with ATAD2 BD construct with an IC50 of 2.7 μM, but does not disrupt full-length ATAD2. GSK8814 suppresses LNCaP colony formation in a soft agar assay by 56% at 20 μM, while its less active diastereomer GSK8815 shows no such effect.
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| Enzyme Assay |
Competitive ligand binding assays are performed using time-resolved fluorescence resonance energy transfer (TR-FRET) with recombinant ATAD2 or ATAD2B bromodomain proteins and a fluorescent tracer. Binding affinity is measured by isothermal titration calorimetry (ITC) to determine pKd values. BROMOScan assays are used for selectivity profiling against a panel of bromodomains.
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| Cell Assay |
Cellular target engagement is assessed by measuring disruption of histone H3.3 interaction with ATAD2 BD construct in intact cells using cellular thermal shift assays or NanoBRET. Colony formation assays are performed in LNCaP cells in soft agar, with colonies counted after 2-3 weeks of treatment with GSK8814 at various concentrations.
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| Animal Protocol |
In vivo animal studies for GSK8814 are primarily conducted in mouse xenograft models of ATAD2-dependent cancers. Tumor-bearing mice are treated with GSK8814 via oral or intraperitoneal administration, with tumor volume measured over time. Pharmacodynamic markers such as ATAD2 target gene expression and bromodomain occupancy are assessed in tumor tissues post-treatment.
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| ADME/Pharmacokinetics |
GSK8814 is aqueous soluble (>439 μM) with good solubility properties. It is stable in powder form and should be stored at −20°C. The compound is soluble in DMSO at 2 mg/mL. Further detailed pharmacokinetic parameters such as half-life, bioavailability, and plasma protein binding are not fully characterized in publicly available literature.
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| Toxicity/Toxicokinetics |
Safety data for GSK8814 indicate it is a research compound that should be handled with standard laboratory safety precautions. Specific toxicological profiles including LD50, organ toxicity, and genotoxicity are not extensively published. As with all active pharmaceutical ingredients, appropriate personal protective equipment should be used during handling.
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| References | |
| Additional Infomation |
GSK8814 is a chemical probe developed by GlaxoSmithKline for epigenetic research. It is not approved for clinical use and is intended for research purposes only. The compound is a first-in-class tool for studying ATAD2 bromodomain function. Its high potency and selectivity make it valuable for validating ATAD2 as a therapeutic target in oncology.
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| Molecular Formula |
C28H35F2N5O3
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|---|---|
| Molecular Weight |
527.6060
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| Exact Mass |
527.27
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| CAS # |
1997369-78-4
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| PubChem CID |
121499171
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.3
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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 |
7
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| Heavy Atom Count |
38
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| Complexity |
850
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| Defined Atom Stereocenter Count |
3
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| SMILES |
FC1(C([H])([H])C([H])([H])C([H])(C([H])([H])O[C@]2([H])C([H])([H])N([H])C([H])([H])[C@@]([H])([C@@]2([H])N([H])C2C3=C(C([H])=C(C([H])([H])[H])C(N3[H])=O)C(C3=C([H])N=C([H])C(C([H])([H])[H])=C3[H])=C([H])N=2)OC([H])([H])[H])C([H])([H])C1([H])[H])F
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| InChi Key |
YDPMMWAOCCOULO-JBRSBNLGSA-N
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| InChi Code |
InChI=1S/C28H35F2N5O3/c1-16-8-19(11-31-10-16)21-12-33-26(24-20(21)9-17(2)27(36)35-24)34-25-22(37-3)13-32-14-23(25)38-15-18-4-6-28(29,30)7-5-18/h8-12,18,22-23,25,32H,4-7,13-15H2,1-3H3,(H,33,34)(H,35,36)/t22-,23+,25+/m0/s1
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| Chemical Name |
8-(((3R,4R,5S)-3-((4,4-difluorocyclohexyl)methoxy)-5-methoxypiperidin-4-yl)amino)-3-methyl-5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1H)-one
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| Synonyms |
GSK8814 GSK-8814 GSK 8814.
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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 (~189.53 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8953 mL | 9.4767 mL | 18.9534 mL | |
| 5 mM | 0.3791 mL | 1.8953 mL | 3.7907 mL | |
| 10 mM | 0.1895 mL | 0.9477 mL | 1.8953 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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