GSK-3326595 Chemical Properties

Boiling point:

760.3±60.0 °C(Predicted)

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)

form 

solid

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.

GSK-3326595 Usage And Synthesis

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.

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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