GSK3368715 2HCl is a novel potent, orally active, reversible type I protein arginine methyltransferases (PRMTs) inhibitor, with IC50 values of 3.1 nM, 48 nM, 1148 nM, 5.7 nM and 1.7 nM for PRMT1, PRMT3, PRMT4, PRMT6, PRMT8, respectively. GSK3368715 induces anti-proliferative effects on cell lines from a broad range of hematological and solid tumor types in vitro. In vivo, GSK3368715 has potent, anti-proliferative activity across cell lines representing a range of solid and hematological malignancies and can completely inhibit tumor growth or cause regressions of tumor models. GSK3368715 dihydrochloride (EPZ019997 dihydrochloride) significantly effects on the growth of BxPC3 xenografts at all doses tested, reducing tumor growth by 78% and 97% in the 150- and 300-mg/kg dose groups, respectively.
|Cell lines||Toledo cells, BxPC3 cells, MiaPaca-2 cells, ACHN cells, MDA-MB-468 cells, RKO cells, Panc03.27 cells, etc.|
|Preparation method||RKO cells are seeded in a clear bottom 384 well plates andtreated with a 20-point two-fold dilution series of GSK3368715 (29,325.5 to 0.03 nM) or 0.15% DMSO. Plates are incubated for 3 days at 37℃ in 5% CO2. Cells are fixed with ice-cold methanol for 30 minutes at room temperature, washed with phosphate buffered saline (PBS), then incubated with Odyssey blocking buffer (Licor) for 1 hour at room temperature.|
|Concentrations||0.75 nM, 2 μM|
|Incubation time||30 min, 3 h - 168 h|
|Animal models||Female NMRI nu/nu mice (NMRI-Foxn1nu) implanted with tumor fragment|
|Dosages||75 mg/kg, 150 mg/kg, 300 mg/kg|
|Solubility (25°C)||DMSO ≥ 100 mg/mL
Water ≥ 90 mg/mL
|Storage||2-8°C, dry, sealed|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
 Andrew Fedoriw, et al. Cancer Cell . Anti-tumor Activity of the Type I PRMT Inhibitor, GSK3368715, Synergizes with PRMT5 Inhibition through MTAP Loss
|Related PRMTs Products|
|AMI-1 disodium salt
AMI-1 is a potent and selective, cell-permeable and reversible inhibitor of protein arginine N-methyltransferases (PRMTs), with IC50 values of 8.8 μM and 3.0 μM for human PRMT1 and yeast-Hmt1p, respectively. AMI-1 is also a potent scavenger of NADPH-oxidase-derived superoxide.
HLCL-61 hydrochloride is a potent and selective, first-in-class protein arginine methyltransferase 5 (PRMT5) inhibitor.
MS049 is a potent and selective inhibitor of PRMT4,6 with IC50 values of 34 nM and 43 nM, respectively.
GSK3326595 is a potent, selective, reversible inhibitor of protein arginine methyltransferase 5 (PRMT5) with an IC50 of 6.2 nM.
MS023 is a potent and selective, cell-active inhibitor of type I PRMTs with IC50s of 4-119 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.