| Identification | Back Directory | [Name]
6-[(1-acetylpiperidin-4-yl)amino]-N-[(2S)-2-hydroxy-3-(1,2,3,4-tetrahydroisoquinolin-2-yl)propyl]pyrimidine-4-carboxamide | [CAS]
1616392-22-3 | [Synonyms]
GSK3326595
EPZ-015938
GSK-3326595,EPZ-015938
EPZ-015938 (GSK3326595)
EPZ015938; EPZ 015938; EPZ-015938
6-[(1-acetylpiperidin-4-yl)amino]-N-[(2S)-2-hydroxy-3-(1
4-tetrahydroisoquinolin-2-yl)propyl]pyrimidine-4-carboxamid
4-Pyrimidinecarboxamide, 6-[(1-acetyl-4-piperidinyl)amino]-N-[(2S)-3-(3,4-dihydro-2(1H)-isoquinolinyl)-2-hydroxypropyl]-
6-[(1-acetylpiperidin-4-yl)amino]-N-[(2S)-2-hydroxy-3-(1,2,3,4-tetrahydroisoquinolin-2-yl)propyl]pyrimidine-4-carboxamide
EPZ015938; 6-[(1-ACETYLPIPERIDIN-4-YL)AMINO]-N-[(2S)-2-HYDROXY-3-(1;2;3;4-TETRAHYDROISOQUINOLIN-2-YL)PROPYL]PYRIMIDINE-4-CARBOXAMID | [Molecular Formula]
C24H32N6O3 | [MDL Number]
MFCD29991177 | [MOL File]
1616392-22-3.mol | [Molecular Weight]
452.55 |
| Chemical Properties | Back Directory | [Boiling point ]
760.3±60.0 °C(Predicted) | [density ]
1.275±0.06 g/cm3(Predicted) | [storage temp. ]
Keep in dark place,Inert atmosphere,2-8°C | [solubility ]
Soluble in DMSO (up to 20 mg/ml). | [form ]
solid | [pka]
12.44±0.46(Predicted) | [color ]
Off-white | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month. |
| Hazard Information | Back Directory | [Description]
GSK3326595 (1616395-22-3) is a potent (IC50?= 6.2nM), selective (>4000-fold over 20 other methyltransferases), SAM uncompetitive, peptide competitive inhibitor of PRMT5.1?PRMT5 inhibition activated the p53 pathway?via?induction of alternative splicing of MDM4 leading to a potent anti-proliferative response both?in vitro?and?in vivo. Combination therapy with palbociclib (CDK4/6 inhibitor, Focus Cat.# 10-4760) and GSK3326595 lead to increased efficacy of palbociclib in treating native and resistant models of melanoma via regulation of the PRMT5-MDM4 axis.2?Currently in clinical trials.3 | [Uses]
GSK-3326595 is a protein arginine methyltransferase 5(PRMT5) inhibitor under clinical trial. | [in vivo]
GSK3326595 (5 mg/kg, Intraperitoneal injection, three times a week for 9?weeks) increased hepatic triglyceride levels without affecting atherosclerosis in LDL receptor knockout mice[3].
GSK3326595 (25-50 mg/kg, Oral, once a day for 2?weeks) enhances the efficacy of anti-programed cell death protein 1 (PD-1) immune checkpoint therapy (ICT) in hepatocellular carcinoma (HCC) in myelocytomatosis transgene turned on (MYC-ON) mice[5]. | Animal Model: | LDL receptor knockout mice[3] | | Dosage: | 5 mg/kg | | Administration: | Intraperitoneal injection (i.p.) | | Result: | Did not alter atherosclerosis susceptibility.
Increased hepatic triglyceride levels without changing the hyperlipidemia extent.
Activated genes involved in fatty acid acquisition. |
| Animal Model: | myelocytomatosis transgene turned on mice[5] | | Dosage: | 25 mg/kg, 50 mg/kg | | Administration: | Oral | | Result: | Significantly suppressed tumor growth at 50 mg/kg.
Showed better therapeutic efficacy at 25 mg/kg. |
| [IC 50]
PRMT5; CDK4; CDK6 | [storage]
Store at -20°C | [References]
1) Gerhart?et al.?(2018),?Activation of the p53-MDM4 regulatory axis defines the anti-tumor response to PRMT5 inhibition through its role in regulating cellular splicing; Sci. Rep.?8?9711
2) AbuHammad?et al.?(2019),?Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma; Proc. Natl. Acad. Sci. USA?116?179909
3) NCT02783300 |
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