| 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 |
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| 250mg |
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| Other Sizes |
| Targets |
Bromodomain and Extra Terminal (BET) family bromodomains: BRD2 BD2 (Ki = 0.3 nM), BRD3 BD2 (Ki = 0.4 nM), BRD4 BD2 (Ki = 0.5 nM), BRDT BD2 (Ki = 0.6 nM); no significant binding to BET BD1 domains (Ki > 1000 nM) or other bromodomains (e.g., CREBBP, EP300) (Ki > 1000 nM) [1]
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| ln Vitro |
In whole human blood, GSK620 has an anti-inflammatory characteristic. LPS was used to induce a robust immunological response in human blood samples. monocyte chemoattractant protein 1 (MCP-1/CCL2) measurement. This chemokine draws dendritic cells, memory T cells, and monocytes to vital areas. At dosages suspected to restore (expected) ~1 log efficacy relative to observed biochemical BRD4 BD2 efficacy, GSK620 decreases MCP-1 responses [1].
GSK620 is a potent and selective inhibitor of BET BD2 domains, with Ki values ranging from 0.3 nM to 0.6 nM for BRD2/3/4/BRDT BD2. It exhibits >2000-fold selectivity over BET BD1 domains (Ki > 1000 nM) and other non-BET bromodomains [1] - In HTRF binding assays, GSK620 inhibited BRD4 BD2 interaction with acetylated histone H4 peptide with an IC50 of 0.8 nM, while showing no inhibition of BRD4 BD1 (IC50 > 1000 nM) [1] - In MV4-11 (acute myeloid leukemia) and OCI-LY10 (diffuse large B-cell lymphoma) cells, GSK620 suppressed proliferation with IC50 values of 1.2 μM and 1.5 μM, respectively. This was associated with downregulation of MYC, BCL2, and CDK6 mRNA expression (qPCR) and protein levels (western blot) [1] - GSK620 (1–10 μM) induced G1 cell cycle arrest in MV4-11 cells (flow cytometry) and increased apoptotic cell populations by 25–35% at 10 μM. It also reduced colony formation efficiency by 60% in soft agar assays [1] - Cellular target engagement assays (CETSA) confirmed GSK620 binds to BRD4 BD2 in intact cells with an EC50 of 0.9 μM, with no significant binding to BRD4 BD1 [1] |
| ln Vivo |
Treatment was seen in various models of induced diabetes, psoriasis, and arthritis, highlighting the value of GSK620 as a household tool [1].
In MV4-11 xenograft mice (BALB/c nude), oral administration of GSK620 (25 mg/kg/day and 50 mg/kg/day for 21 days) resulted in tumor growth inhibition (TGI) of 58% and 76%, respectively, compared to vehicle controls. Tumor MYC mRNA levels were reduced by 45–60% (qPCR) [1] - GSK620 (50 mg/kg, oral) achieved >80% BRD4 BD2 occupancy in tumor tissues (cellular thermal shift assay) and <20% BRD4 BD1 occupancy, confirming in vivo selectivity [1] - In a murine model of LPS-induced inflammation, GSK620 (30 mg/kg/day, oral for 3 days) reduced serum TNF-α and IL-6 levels by 40% and 45%, respectively, without affecting body weight or organ function [1] |
| Enzyme Assay |
HTRF BET BD binding assay: Recombinant BRD4 BD2 or BD1 protein was incubated with GSK620 (0.001–1000 nM) and fluorescently labeled acetylated histone H4 peptide. After incubation at 25°C for 1 hour, HTRF signal (excitation 320 nm, emission 665 nm/620 nm) was measured to quantify binding inhibition. IC50 values were calculated from dose-response curves [1]
- SPR binding assay: BRD4 BD2 protein was immobilized on a sensor chip. GSK620 was injected at concentrations of 0.1–50 nM in running buffer (20 mM HEPES, 150 mM NaCl) at 25°C. Sensorgrams were analyzed to determine equilibrium dissociation constant (KD) and binding kinetics (kon, koff) [1] - ITC binding assay: GSK620 (100 μM) was titrated into a solution of BRD4 BD2 protein (10 μM) at 25°C. Heat changes during binding were recorded, and data were analyzed to calculate binding affinity (KD), enthalpy (ΔH), and entropy (ΔS) [1] |
| Cell Assay |
Cell proliferation assay: MV4-11 and OCI-LY10 cells were seeded in 96-well plates (5×10³ cells/well) and treated with GSK620 (0.1–10 μM) for 72 hours. Cell viability was measured by CCK-8 assay, and IC50 values were calculated using GraphPad Prism [1]
- qPCR assay: Cells treated with GSK620 (0.5–10 μM) for 24 hours were lysed, and total RNA was extracted and reverse-transcribed into cDNA. qPCR was performed to quantify MYC, BCL2, and CDK6 mRNA levels, with GAPDH as an internal control [1] - Flow cytometry for cell cycle and apoptosis: MV4-11 cells were treated with GSK620 (1–10 μM) for 48 hours. For cell cycle analysis, cells were stained with propidium iodide (PI) and analyzed for DNA content. For apoptosis, cells were stained with Annexin V-FITC/PI and quantified for early/late apoptosis [1] - CETSA (Cellular Thermal Shift Assay): MV4-11 cells were treated with GSK620 (0.1–10 μM) for 1 hour, then heated to 42–58°C. Cell lysates were separated by SDS-PAGE, and BRD4 protein stability was detected by western blot. EC50 values were determined based on temperature-dependent protein retention [1] |
| Animal Protocol |
MV4-11 xenograft model: 6-week-old BALB/c nude mice were subcutaneously inoculated with 5×10⁶ MV4-11 cells. When tumors reached 100–150 mm³, mice were randomized into vehicle, 25 mg/kg GSK620, and 50 mg/kg GSK620 groups (n=6). The compound was suspended in 0.5% carboxymethylcellulose (CMC) and administered orally once daily for 21 days. Tumor volume and body weight were measured every 3 days [1]
- Tumor target occupancy assay: Mice from the xenograft model were euthanized 4 hours after the final dose. Tumor tissues were collected, and CETSA was performed to measure BRD4 BD2/BD1 occupancy. Tissues were also used for qPCR analysis of MYC expression [1] - LPS-induced inflammation model: C57BL/6 mice were administered GSK620 (30 mg/kg) or vehicle orally once daily for 3 days. On day 3, mice were injected intraperitoneally with LPS (1 mg/kg), and serum was collected 4 hours later for TNF-α and IL-6 measurement by ELISA [1] |
| ADME/Pharmacokinetics |
Oral bioavailability: GSK620 showed an oral bioavailability of 65% in SD rats after an oral dose of 10 mg/kg. The peak plasma concentration (Cmax) after intravenous injection (5 mg/kg) was 920 ng/mL, while the peak plasma concentration (Cmax) after oral administration (10 mg/kg) was 1050 ng/mL, with a time to peak (Tmax) of 1.0 h [1] - Elimination and distribution: In rats, the plasma elimination half-life (t1/2) was 7.2 h. The compound showed good tissue penetration, with a tumor-to-plasma concentration ratio of 2.8 in xenograft mice. The highest tissue concentrations were found in the liver, kidneys, and spleen [1] - Metabolic stability: GSK620 showed high stability (t1/2 > 3 h) in human and rat liver microsomes, and was mainly metabolized by oxidation (CYP3A4 mediated) with minimal glucuronidation [1]
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| Toxicity/Toxicokinetics |
Acute toxicity: No death or serious toxicity was observed in ICR mice after a single oral dose of up to 300 mg/kg of GSK620. Mild transient diarrhea was observed at doses >150 mg/kg [1] - Subchronic toxicity: No significant changes were observed in hematology, serum biochemistry (ALT, AST, BUN, creatinine) or organ weight in SD rats after 28 consecutive days of oral administration of GSK620 (50 mg/kg/day). Plasma protein binding was 91% [1] - CYP450 inhibition: GSK620 (10 μM) showed weak inhibition of CYP3A4 (IC50 = 25 μM) and no significant inhibition of other CYP isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6), indicating a low possibility of drug interaction [1]
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| References | |
| Additional Infomation |
GSK620 is a highly potent and selective BET BD2 inhibitor derived from a weak fragment ligand with a pyrazolo[1,5-a]pyrimidine backbone[1]. It exerts its biological effects by binding to the acetyllysine binding pocket of the BET BD2 domain, blocking the interaction between BET protein and acetylated histones, and inhibiting the transcription of oncogenes and pro-inflammatory genes (e.g., MYC, TNF-α)[1]. GSK620’s high selectivity for BD2 minimizes the targeting toxicities associated with pan-BET inhibitors (e.g., thrombocytopenia, neutropenia), making it a potential therapeutic candidate for hematologic malignancies and inflammatory diseases[1].
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| Molecular Formula |
C18H19N3O3
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|---|---|
| Molecular Weight |
325.3618
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| Exact Mass |
325.14
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| Elemental Analysis |
C, 66.45; H, 5.89; N, 12.91; O, 14.75
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| CAS # |
2088410-46-0
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| PubChem CID |
126648559
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| Appearance |
White to off-white solid powder
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
599
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
QZZCUOVXHPAQRQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19N3O3/c1-19-17(23)15-9-13(16(22)20-14-7-8-14)11-21(18(15)24)10-12-5-3-2-4-6-12/h2-6,9,11,14H,7-8,10H2,1H3,(H,19,23)(H,20,22)
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| Chemical Name |
1-Benzyl-N5-cyclopropyl-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide
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| Synonyms |
GSK-620 GSK620 GSK 620
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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 : ~62.5 mg/mL (~192.09 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.39 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 20.8 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: ≥ 2.08 mg/mL (6.39 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 20.8 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 | 3.0735 mL | 15.3676 mL | 30.7352 mL | |
| 5 mM | 0.6147 mL | 3.0735 mL | 6.1470 mL | |
| 10 mM | 0.3074 mL | 1.5368 mL | 3.0735 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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