Molecular Weight (MW)

489.91

Formula

C26H20ClN3O5

CAS No.

1346607-05-3

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 97 mg/mL (198.0 mM)

Water:<1 mg/mL

Ethanol:<1 mg/mL

Solubility (In vivo)

2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL

Other info

Synonym: GSK-621; GSK621; GSK 621.

Chemical Name: 6-chloro-5-(2'-hydroxy-3'-methoxy-[1,1'-biphenyl]-4-yl)-3-(3-methoxyphenyl)-1,5-dihydro-2H-pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione

InChi Key: KURYSXLJGKKDHT-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H20ClN3O5/c1-34-18-6-3-5-17(13-18)30-25(32)23-20(28-26(30)33)14-22(27)29(23)16-11-9-15(10-12-16)19-7-4-8-21(35-2)24(19)31/h3-14,31H,1-2H3,(H,28,33)

SMILES Code: O=C1NC2=C(N(C3=CC=C(C4=CC=CC(OC)=C4O)C=C3)C(Cl)=C2)C(N1C5=CC=CC(OC)=C5)=O

In Vitro

In vitro activity: In AML cell lines and primary AML samples, GSK621 markedly increases phosphorylation at AMPKα T172, a marker of AMPK activation. In a set of 20 cell lines, GSK621 reduces the proliferation of all 20 lines with IC50 ranged from 13-30 μM, and increases apoptosis in 17 (85%) lines. In addition, GSK621 also triggers autophagy, which partially contributes to AML cell death.

Kinase Assay: HEPG2 cells are treated with increasing doses of A-769662 or GSK621, and ACC S79 phosphorylation is assessed as a surrogate marker for AMPK activation using a commercially available ELISA kit.

Cell Assay: Twenty AML cell lines (MV4-11, OCI-AML3, OCI-AML2, HL-60, Kasumi, HEL, UT7, NB4, TF-1, KG1A, Nomo p28, SKM-1, U937, YHP1, MOLM-14, Mo7e, K562, MOLM-13, EOL-1, SET-2 cell lines) are treated with log10 dilutions of GSK621 and relative viability is determined by CellTiter-Glo?assay. IC50 of GSK621 among these 20 cell lines is calculated using the Prism software and are presented as log[C] with [C] in mol/l (M). Results are presented for 5 different cell lines per panel.

In Vivo

In nude mice bearing MOLM-14 xenografts, GSK621 (30 mg/kg, i.p.) reduces leukemia growth and significantly extends survival by enhancing AMPK activity and the induction of apoptosis.

Animal model

In animals with xenograft MOLM-14 cells

Formulation & Dosage

30 mg/kg; i.p. injection.

References

Cell Rep. 2015 Jun 9;11(9):1446-57.