1616392-22-3

Basic information

• Product Name: GSK-3326595
• Synonyms: 6-[(1-acetylpiperidin-4-yl)amino]-N-[(2S)-2-hydroxy-3-(1,2,3,4-tetrahydroisoquinolin-2-yl)propyl]pyrimidine-4-carboxamide;GSK3326595;EPZ-015938;4-Pyrimidinecarboxamide, 6-[(1-acetyl-4-piperidinyl)amino]-N-[(2S)-3-(3,4-dihydro-2(1H)-isoquinolinyl)-2-hydroxypropyl]-;GSK-3326595,EPZ-015938;EPZ-015938 (GSK3326595)
• CAS NO: 1616392-22-3
• Molecular Formula: C24H32N6O3
• Molecular Weight: 452.54928
• Product Categories: API
• Mol File: 1616392-22-3.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 760.3±60.0 °C(Predicted)
• Appearance: /
• Density: 1.275±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Soluble in DMSO (up to 20 mg/ml).
• PKA: 12.44±0.46(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
• CAS DataBase Reference: GSK-3326595(CAS DataBase Reference)
• NIST Chemistry Reference: GSK-3326595(1616392-22-3)
• EPA Substance Registry System: GSK-3326595(1616392-22-3)

Safety Data

• Hazardous Substances Data: 1616392-22-3(Hazardous Substances Data)

Usage

Description

GSK-3326595 is a potent, selective, and uncompetitive inhibitor of protein arginine methyltransferase 5 (PRMT5). It exhibits high potency with an IC50 of 6.2 nM and is more than 4000-fold selective over 20 other methyltransferases. GSK-3326595 functions as a SAM uncompetitive and peptide competitive inhibitor, leading to the activation of the p53 pathway through the induction of alternative splicing of MDM4. This results in a potent anti-proliferative response both in vitro and in vivo.

Uses

Used in Pharmaceutical Industry:
GSK-3326595 is used as a PRMT5 inhibitor for the treatment of various types of cancer. Its inhibition of PRMT5 activates the p53 pathway, which plays a crucial role in preventing the development of cancer by promoting the repair of damaged DNA or initiating apoptosis in cells with excessive DNA damage. The compound is currently under clinical trial.
Used in Combination Therapy:
GSK-3326595 is used in combination therapy with palbociclib (CDK4/6 inhibitor) to increase the efficacy of palbociclib in treating native and resistant models of melanoma. This combination therapy works by regulating the PRMT5-MDM4 axis, enhancing the anti-proliferative response and potentially improving treatment outcomes for patients with melanoma.

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

Upstream product

• 1616077-51-0 (S)-1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)-propan-2-ol 
• 1616064-77-7 (R)-2-(oxiran-2-ylmethyl)-1,2,3,4-tetrahydroisoquinoline 
• 263270-52-6 6-chloropyrimidine-4-carbonyl chloride 
• 6299-87-2 6-hydroxypyrimidine-4-carboxylic acid 
• 160357-94-8 1-(4-amino-piperidin-1-yl)-ethanone 
• 91-21-4 1,2,3,4-tetrahydroisoquinoline 

Relevant articles and documents

CRYSTALLINE SALTS OF (S)-6-((1-ACETYLPIPERIDIN-4-YL)AMINO)-N-(3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YL)-2-HYDROXYPROPYL)PYRIMIDINE-4-CARBOXAMIDE

Disclosed are novel crystalline salts of (S)-6-((1-acetylpiperidin-4-yl)amino)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide and pharmaceutical compositions containing the same. Also disclosed are processes for the prepar