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Chemical Structure| 1616392-22-3 Chemical Structure| 1616392-22-3
Chemical Structure| 1616392-22-3

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CAS No.: 1616392-22-3

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GSK3326595 is a protein arginine methyltransferase 5 (PRMT5) inhibitor that decreases SARS-CoV-2 infection, inhibits cancer cell proliferation, induces pro-inflammatory macrophage polarization, and increases hepatic triglyceride levels without affecting atherosclerosis. It is used in research on relapsed/refractory mantle cell lymphoma.

Synonyms: EPZ015938; Pemrametostat

4.5 *For Research Use Only !

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Product Details of GSK3326595

CAS No. :1616392-22-3
Formula : C24H32N6O3
M.W : 452.55
SMILES Code : O=C(C1=NC=NC(NC2CCN(C(C)=O)CC2)=C1)NC[C@H](O)CN3CC4=C(C=CC=C4)CC3
Synonyms :
EPZ015938; Pemrametostat
MDL No. :MFCD29991177
InChI Key :JLCCNYVTIWRPIZ-NRFANRHFSA-N
Pubchem ID :90241742

Safety of GSK3326595

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of GSK3326595

epigenetics

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description Reference
MC38/gp100 and B16 tumor cells 40nM to 10 μM 5 days Inhibits tumor cell growth PMC11418539
Z-138 cells 2.5 nM 3 days Determine the cellular EC50 of SDMA inhibition PMC6018746
Z-138 cells 200 nM 3 days Evaluate cell cycle distribution PMC6018746
MCF-7 cells 200 nM 7 days Evaluate cell cycle distribution PMC6018746
HT-29 cells 1 μM 5 days To evaluate the effect of MTDIA and AG-270 on HT-29 cell growth, the results showed that the combination of MTDIA and AG-270 significantly inhibited cell growth and induced apoptosis. PMC10770533
peritoneal macrophages 100 μM 24 hours GSK3326595 pre-treatment primed peritoneal macrophages to obtain a pro-inflammatory phenotype upon IFN-γ stimulation, evidenced by increased iNOS and IP-10 expression levels. PMC10098290
HEK-293T cells 100 nM 48 hours GSK3326595 dramatically decreased interaction between ACE2 and the RBD PMC9537780
A549 cells 100 nM GSK3326595 significantly decreased ACE2 SDMA modification PMC9537780
CAL-1 cells 0.001, 0.005, 0.02, 0.08, 0.31, 1.25, 5 μM 72 hours To evaluate the effect of GSK3326595 on the growth of CAL-1 cells, the results showed that GSK3326595 significantly inhibited the growth of CAL-1 cells and induced apoptosis. PMC9631685
A375AR cells 500 nM 6 days Inhibit PRMT5 activity, restore sensitivity to palbociclib PMC6731642
HT144AR cells 250 nM 6 days Inhibit PRMT5 activity, restore sensitivity to palbociclib PMC6731642
A375 cells 500 nM 6 days Enhance the efficacy of palbociclib PMC6731642
HT144 cells 250 nM 6 days Enhance the efficacy of palbociclib PMC6731642
Pancreatic cancer cells 20μM 72 hours GSK3326595 inhibits PRMT5 activity, re-activates the dysregulated Hippo signaling pathway, and inhibits the growth of pancreatic cancer cells. PMC10690468

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description Reference
MYC-ON mice HCC xenograft models 50 mg/kg/day significantly suppressed tumor growth compared with anti–PD-1 monotherapy PMC9942701
C57BL/6 mice MC38/gp100 Mtap-KO or B16 Mtap-KO tumor models Oral 30 mg/kg/day Once per day for the duration of the study Superior antitumor activity in combination with anti-PD-1 PMC11418539
Mice Z-138 xenograft model Oral 100 mg/kg Twice daily for 21 days Assess the anti-tumour activity of GSK3326595 PMC6018746
NOD/SCID mice NOD/SCID mice Oral 100 mg/kg Once daily for 20 days To evaluate the effect of GSK3326595 on tumor growth in NOD/SCID mice, the results showed that GSK3326595 significantly inhibited tumor growth and induced apoptosis in normal gut cells. PMC10770533
Mice LDL receptor knockout mice Intraperitoneal injection 5 mg/kg 3 times per week for 9 weeks Chronic GSK3326595 treatment did not alter the inflammatory state or atherosclerosis susceptibility in mice, but significantly increased hepatic triglyceride levels. PMC10098290
NSG mice CAL-1 xenograft model Oral 150 mg/kg Twice daily until humane endpoint To evaluate the effect of GSK3326595 on tumor growth in the CAL-1 xenograft model, the results showed that GSK3326595 significantly inhibited tumor growth and reduced SDMA-modified protein levels. PMC9631685
BALB/c Nude mice A375 tumor xenograft model Oral 100 mg/kg Daily until tumor progression Delay the emergence of palbociclib resistance, enhance therapeutic efficacy PMC6731642
Immunodeficient mice Pancreatic cancer xenograft model Intravenous injection 100 mg/kg Every 3 days for 30 days GSK3326595 significantly impeded the progression of pancreatic cancer, re-activated the Hippo signaling pathway, and inhibited tumor growth. PMC10690468
Mice B16 and YUMM1.7 melanoma models Oral 40 mg/kg QD, from day 10 Combination of GSK3326595 with anti-PD1 antibody therapy enhanced the anti-tumor response, reflected in reduced tumor size. PMC7508354

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT04676516 Breast Cancer PHASE2 COMPLETED 2022-08-15 St. Joseph's Health Care Londo... More >>n, London, Ontario, N6A 4V2, Canada Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.21mL

0.44mL

0.22mL

11.05mL

2.21mL

1.10mL

22.10mL

4.42mL

2.21mL

References

 

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