Introduction：Basic information about CAS 1346572-63-1|GSK503, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | GSK503 |
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| CAS Number | 1346572-63-1 | Molecular Weight | 526.672 |
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| Density | 1.2±0.1 g/cm3 | Boiling Point | 798.6±60.0 °C at 760 mmHg |
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| Molecular Formula | C31H38N6O2 | Melting Point | / |
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| MSDS | / | Flash Point | 436.8±32.9 °C |
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Names
| 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 |
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| Synonym | More Synonyms |
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GSK503 BiologicalActivity
| Description | GSK503 is a potent and specific inhibitor of EZH2 methyltransferase with Kiapp values of 3 to 27 nM. |
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| Related Catalog | Signaling Pathways >>Epigenetics >>Epigenetic Reader DomainSignaling Pathways >>Epigenetics >>Histone MethyltransferaseResearch Areas >>Cancer |
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| Target | Ki: 3 to 27 nM (EZH2)[1] |
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| 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]. |
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| 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]. |
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| 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]. |
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| References | [1]. Béguelin W, et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell. 2013 May 13;23(5):677-92. [2]. Zingg D, et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun. 2015 Jan 22;6:6051. |
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Chemical & Physical Properties
| Density | 1.2±0.1 g/cm3 |
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| Boiling Point | 798.6±60.0 °C at 760 mmHg |
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| Molecular Formula | C31H38N6O2 |
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| Molecular Weight | 526.672 |
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| Flash Point | 436.8±32.9 °C |
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| Exact Mass | 526.305603 |
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| LogP | 3.30 |
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| Vapour Pressure | 0.0±2.8 mmHg at 25°C |
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| Index of Refraction | 1.648 |
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| InChIKey | HRDQQHUKUIKFHT-UHFFFAOYSA-N |
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| SMILES | Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(N4CCN(C)CC4)nc3)cc3c2c(C)cn3C(C)C)c(=O)[nH]1 |
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| Storage condition | -20℃ |
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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 |
