1346572-63-1
1346572-63-1 structure
- Name: GSK503
- Chemical Name: N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-1H-indole-4-carboxamide
- CAS Number: 1346572-63-1
- Molecular Formula: C31H38N6O2
- Molecular Weight: 526.672
- Catalog: Signaling Pathways Epigenetics Epigenetic Reader Domain
- Create Date: 2018-12-21 18:37:25
- Modify Date: 2024-01-02 12:35:13
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GSK503 is a potent and specific inhibitor of EZH2 methyltransferase with Kiapp values of 3 to 27 nM.
| Name | N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-1H-indole-4-carboxamide |
|---|---|
| Synonyms |
1H-Indole-4-carboxamide, N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-
N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-isopropyl-3-methyl-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-1H-indole-4-carboxamide GSK-503 GSK503 |
| Description | GSK503 is a potent and specific inhibitor of EZH2 methyltransferase with Kiapp values of 3 to 27 nM. |
|---|---|
| Related Catalog | |
| Target |
Ki: 3 to 27 nM (EZH2)[1] |
| In Vitro | GSK503 inhibits the methyltransferase activity of wild type and mutant EZH2 with similar potency (Kiapp=3-27 nM) and is structurally related to GSK126 and GSK343. GSK503 is >200 fold selective over EZH1 (Kiapp=636 nM) and >4000 fold selective over other histone methyltransferases[1]. |
| In Vivo | In a melanoma mouse model, conditional EZH2 ablation as much as treatment with the GSK503 stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology[2]. GSK503 displays favorable pharmacokinetics in mice. GSK503, but not vehicle, prevents the formation of germinal center after SRBC or NP-KLH immunization, phenocopying the Ezh2 null phenotype. GSK503 treatment leads to reduced numbers of GC B-cells by flow cytometry, reduces number and volume of GCs by immunohistochemistry, and impairs formation high affinity antibodies[1]. |
| Animal Admin | Mice: To pharmacologically inhibit Ezh2 activity, Tyr::N-RasQ61K Ink4a-/- and C57Bl/6 mice are subjected to treatment with GSK503, which is diluted (15 mg/mL) in 20% Captisol solution. Efficient Ezh2 inhibition is achieved by daily intraperitoneal injections of 150 mg/kg GSK503 over 35 consecutive days. Mice are monitored during and after treatment to measure GSK503-induced reversible weight loss. C57Bl/6 and Foxn1nu/nu mice engrafted with melanoma cells are subjected to TM and GSK503 treatment as described above[2]. |
| References |
| Density | 1.2±0.1 g/cm3 |
|---|---|
| Boiling Point | 798.6±60.0 °C at 760 mmHg |
| Molecular Formula | C31H38N6O2 |
| Molecular Weight | 526.672 |
| Flash Point | 436.8±32.9 °C |
| Exact Mass | 526.305603 |
| LogP | 3.30 |
| Vapour Pressure | 0.0±2.8 mmHg at 25°C |
| Index of Refraction | 1.648 |
| Storage condition | -20℃ |