GSK699
Based on 1 Customer Validation
GSK699 is a KAT2A/B/PCAF/GCN5 PROTAC degrader. GSK699 induces proteasome-dependent degradation of KAT2A, KAT2B, PCAF and GCN5, regulates the histone acetyltransferase activity of the SAGA complex, and reduces the level of histone H3K9ac. GSK699 inhibits the growth of neuroblastoma, acute myeloid leukemia and small cell lung cancer cells. GSK699 reduces the production of inflammatory cytokines and chemokines, and impairs LPS-stimulated immune cell responses. GSK699 is applicable to research related to acute myeloid leukemia, small cell lung cancer, neuroblastoma and inflammatory diseases.
(Pink: GCN5/PCAF ligand (HY-101027); Blue: Cereblon ligand (HY-103596); Black: linker).
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 99.87%
- CAS 番号: 2260944-68-9
- 分子式: C45H51BrN8O7
- 分子量:895.84
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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生物活性
製品説明
IC50 & Target
[1]|
IL-6 |
GCN5/PCAF |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| THP-1 | DC50 |
1.5 nM
Compound: 92; GSK983
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Protac activity against E3 ubiquitin ligase/PCAF in human THP-1 cells assessed as induction of PCAF protein degradation
Protac activity against E3 ubiquitin ligase/PCAF in human THP-1 cells assessed as induction of PCAF protein degradation
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[PMID: 31035238] |
| THP-1 | DC50 |
3 nM
Compound: 92; GSK983
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Protac activity against E3 ubiquitin ligase/GCN5 in human THP-1 cells assessed as induction of GCN5 protein degradation
Protac activity against E3 ubiquitin ligase/GCN5 in human THP-1 cells assessed as induction of GCN5 protein degradation
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[PMID: 31035238] |
体外実験
GSK699 potently degrades KAT2A (DC50 = 2.2 nM) and KAT2B (DC50 = 0.08 nM) in MOLM-13 cells, and inhibits the proliferation of MOLM-13 cells with an activity of GI50 = 64 nM[1].
GSK699 potently degrades KAT2A (DC50 = 1.5 nM) and KAT2B (DC50 = 0.1 nM) in NCI-H1048 cells, and inhibits the proliferation of NCI-H1048 cells with a GI50 of 32 nM[1].
GSK699 inhibits the proliferation of KELLY neuroblastoma cells in vitro[1].
Treatment of wild-type primary mouse HSPCs with GSK699 (100 nM; 48 h) significantly reduces intracellular H3K9ac levels, upregulates cell surface Sca-1 expression, and increases the frequency of immunophenotypic HSCs and megakaryocyte progenitor cells[2].
Treatment of c-Kit+ Sca-1+Lin− wild-type primary mouse hematopoietic stem and progenitor cells (HSPCs) with GSK699 (100 nM; 48 h) induces transcriptomic changes that are highly correlated with those caused by Tada2b knockout in HSPCs[2].
GSK699 (0.03-1000 nM; 18 h) potently induces concentration-dependent degradation of PCAF in THP1 cells[3].
GSK699 (100 nM; 5-6 days) potently reduces the production of IL-6, IL-12p70, IL-10, IL-1β, IFN-γ, TNF and IL-8 in human monocyte-derived dendritic cells stimulated with LPS (HY-D1056)[3].
GSK699 (100 nM; 6 days) reduces the production of multiple inflammatory mediators in LPS-stimulated human monocyte-derived dendritic cells, including IL-6, CXCL12, IL12A, TNF, IL-12p70, IL10, CXCL1/GROα, CXCL11/I-TAC, CCL16, CCL7, CCL20/MIP-3α, CXCL10, CXCL1, CCL8 and CCL19/MIP-3β, and upregulates CD1C, FCER1A, CD28 and CD8A[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:THP1 human monocytic leukemia cells
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Concentration:0.03 nM, 0.1 nM, 0.3 nM, 1 nM, 3 nM, 10 nM, 30 nM, 100 nM, 300 nM, 1000 nM
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Incubation Time:18 h
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Result:Induced potent, concentration-dependent degradation of PCAF in THP1 cells.
Left 65% of PCAF remaining relative to DMSO control at 0.03 nM.
Left 62% of PCAF remaining relative to DMSO control at 0.1 nM.
Left 53% of PCAF remaining relative to DMSO control at 0.3 nM.
Left 29% of PCAF remaining relative to DMSO control at 1 nM.
Left 16% of PCAF remaining relative to DMSO control at 3 nM.
Left 8% of PCAF remaining relative to DMSO control at 10 nM.
Left 4% of PCAF remaining relative to DMSO control at 30 nM.
Left 3% of PCAF remaining relative to DMSO control at 100 nM.
Left 3% of PCAF remaining relative to DMSO control at 300 nM.
Left 6% of PCAF remaining relative to DMSO control at 1000 nM.
Showed a slight hook effect (increased remaining PCAF) at the highest concentration (1000 nM).
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Cell Line:LPS-stimulated human CD14+ monocyte-derived dendritic cells (DCs)
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Concentration:100 nM
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Incubation Time:6 days (differentiation)
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Result:Altered LPS-induced mRNA expression of numerous genes in human monocyte-derived dendritic cells.
Significantly down-regulated chemokine and cytokine genes including CXCL12, IL6, IL12A, IL10, CCL16, CCL7, CXCL10, CXCL1, and CCL8.
Increased CD1C, FCER1A, CD28, and CD8A mRNA levels.
Significantly down-regulated TNF mRNA but by less than 3-fold.
Parmacokinetics
| Species | Dose | Route | CL | CLunbound | T1/2 | Vdss | AUC0-last |
|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 36 mL/min/kg | 27692 mL/min/kg | 1.4 h | 1.2 L/kg | 0.00062 nM·h/mL |
化学情報
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CAS 番号 2260944-68-9
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性状 Solid
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分子量 895.84
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分子式 C45H51BrN8O7
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Color Light yellow to yellow
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SMILES
O=C(N(CCCN(C1=CC=C(CCCOC2=CC=CC(C(N3C(CC4)C(NC4=O)=O)=O)=C2C3=O)C=C1)C)C)C5=CC=C([C@@H]6CN(C)C[C@H](NC(C=NN7C)=C(Br)C7=O)C6)C=C5
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
体外:
DMSO : 50 mg/mL (55.81 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
体内:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.79 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.79 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2.5 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
プロトコル
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LPS-Induced Endotoxemia/Systemic Inflammation
Lipopolysaccharide (LPS)-induced endotoxemia is a widely used in vivo model of acute systemic inflammation in which LPS, a Gram-negative bacterial endotoxin, activates innate immune signaling primarily through TLR4, leading to rapid and transient induction of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and tissues. This cytokine surge is commonly used as a measurable readout of systemic inflammatory activation and immune dysregulation, and is typically assessed within hours after intraperitoneal LPS administration in mouse models of endotoxemia. The model captures key features of systemic inflammatory response syndrome, including cytokine release, immune cell activation, and downstream tissue responses, and has been used to evaluate anti-inflammatory interventions such as cytokine modulation, lipid mediators, and immune cell-targeting therapies.
純度とドキュメンテーション
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データシート (276 KB)
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取扱説明書 (2659 KB)
参考文献
[1]. Neef J, et al. Discovery and Optimization of Orally Bioavailable Heterobifunctional Degraders of KAT2A/B for the Treatment of Cancer. J Med Chem. 2026;69(4):4548-4566. [Content Brief]
[2]. Haney MS, et al. In vivo CRISPR screening identifies SAGA complex members as key regulators of hematopoiesis. bioRxiv [Preprint]. 2025 May 19:2022.07.22.501030. [Content Brief]
[3]. Bassi ZI, et al. Modulating PCAF/GCN5 Immune Cell Function through a PROTAC Approach. ACS Chem Biol. 2018;13(10):2862-2867. [Content Brief]
[4]. Luo H, et al. Advancing Design Strategy of PROTACs for Cancer Therapy. MedComm (2020). 2025;6(7):e70258. Published 2025 Jun 25. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1163 mL | 5.5814 mL | 11.1627 mL | 27.9068 mL |
| 5 mM | 0.2233 mL | 1.1163 mL | 2.2325 mL | 5.5814 mL | |
| 10 mM | 0.1116 mL | 0.5581 mL | 1.1163 mL | 2.7907 mL | |
| 15 mM | 0.0744 mL | 0.3721 mL | 0.7442 mL | 1.8605 mL | |
| 20 mM | 0.0558 mL | 0.2791 mL | 0.5581 mL | 1.3953 mL | |
| 25 mM | 0.0447 mL | 0.2233 mL | 0.4465 mL | 1.1163 mL | |
| 30 mM | 0.0372 mL | 0.1860 mL | 0.3721 mL | 0.9302 mL | |
| 40 mM | 0.0279 mL | 0.1395 mL | 0.2791 mL | 0.6977 mL | |
| 50 mM | 0.0223 mL | 0.1116 mL | 0.2233 mL | 0.5581 mL |
GSK699 関連分類
HY-122822 関連分類
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Keywords
- GSK699
- 2260944-68-9
- GSK 699
- GSK-699
- PROTACs
- Histone Acetyltransferase
- Interleukin Related
- CXCR
- TNF Receptor
- CD28
- KAT2A/B/PCAF/GCN5 PROTAC degrader
- acute myeloid leukemia
- small cell lung cancer
- neuroblastoma
- MOLM-13 cells
- NCI-H1048 cells
- KELLY neuroblastoma cells
- HSPCs
- human monocyte-derived dendritic cells
- Inhibitor
- inhibitor
- inhibit