| Identification | Back Directory | [Name]
EPZ015666 | [CAS]
1616391-65-1 | [Synonyms]
EPZ015666
GSK3235025
GSK-3235025
N-[(2S)-3-(3,4-Dihydro-2(1H)-isoquinolinyl)-2-hydroxypropyl]-6-(3-oxetanylamino)-4-pyrimidinecarboxamide
(S)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-6-(oxetan-3-ylamino)pyrimidine-4-carboxamide
N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-6-(oxetan-3-ylamino)pyrimidine-4-carboxamide | [Molecular Formula]
C20H25N5O3 | [MDL Number]
MFCD28411588 | [MOL File]
1616391-65-1.mol | [Molecular Weight]
383.44 |
| Chemical Properties | Back Directory | [Melting point ]
124-131°C | [Boiling point ]
686.4±55.0 °C(Predicted) | [density ]
1.331±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
Soluble in DMSO (up to 20 mg/ml) | [form ]
powder | [pka]
12.40±0.46(Predicted) | [color ]
white to beige | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | [CAS DataBase Reference]
1616391-65-1 |
| Hazard Information | Back Directory | [Uses]
Protein arginine methyltransferases (PRMTs) target nuclear and cytoplasmic substrates and can alter protein actions and gene expression. PRMT5, which can methylate histones H2A, H3, and H4, ribonucleoproteins, and other proteins, is upregulated in several human cancers, including lymphomas. Moreover, suppression of PRMT5 expression induces lymphoma cell death. EPZ015666 is a potent, orally bioavailable inhibitor of PRMT5 (Ki = 5 nM). It displays more than 20,000-fold selectivity for PRMT5 over other PMTs. EPZ015666 acts by blocking the association of PRMT5 with methylosome protein 50, which is necessary for the formation of an active methyltransferase complex. EPZ015666 (100 mg/kg twice daily) blocks the growth of mantle cell lymphoma Z-138 xenografts, without significant body weight loss, in mice.[Cayman Chemical] | [Biochem/physiol Actions]
EPZ015666 (GSK3235025) is a protein arginine methyltransferase PRMT5 inhibitor with an IC50 value of of 22 nM in biochemical assays and no inhibition up to the maximum tested concentration of 50 μM against a panel of 20 other protein methyltransferases. Inhibition was uncompetitive with respect to SAM. EPZ015666 showed dose-dependent antitumor activity in multiple in vitro and in vivo mantle cell lymphoma (MCL) models with treatment of MCL cell lines leading to inhibition of SmD3 methylation and cell death. | [storage]
Store at -20°C |
| Questions And Answer | Back Directory | [Description]
EPZ015666 (GSK3235025) is an orally available inhibitor of protein arginine methyltransferase-5 (PRMT5), which is involved in diverse cellular processes, including tumorigenesis, and its overexpression is observed in cell lines and primary patient samples derived from lymphomas, particularly mantle cell lymphoma (MCL).EPZ015666 showed dose-dependent antitumor activity in multiplein vitroandin vivomantle cell lymphoma (MCL) models with treatment of MCL cell lines leading to inhibition of SmD3 methylation and cell death. Therefore, it is a potential drug candidate for future cancer therapy.
| [References]
Chan-Penebre, E, et al. "A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models." Nature Chemical Biology 11.6(2015):432.
Duncan, K. W., et al. "Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666." Acs Medicinal Chemistry Letters 7.2(2016):162-166.
http://www.sigmaaldrich.com/catalog/product/sigma/sml1421?lang=en®ion=US
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