SML2003

GSK621

≥98% (HPLC)

• Synonym(s): 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, 6-Chloro-5-(2′-hydroxy-3′-methoxy[1,1′-biphenyl]-4-yl)-3-(3-methoxyphenyl)-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione
• Empirical Formula (Hill Notation): C₂₆H₂₀ClN₃O₅
• CAS Number: 1346607-05-3
• Molecular Weight: 489.91
• MDL number: MFCD28502280
• UNSPSC Code: 51111800
• NACRES: NA.77

Properties

• Assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: 2-8°C
• SMILES string: O=C(NC1=C2N(C3=CC=C(C4=C(O)C(OC)=CC=C4)C=C3)C(Cl)=C1)N(C5=CC=CC(OC)=C5)C2=O

Description

Application

GSK621 has been used as an AMP-activated kinase α (AMPK α) activator to study the antiviral role of AMPK in Zika virus (ZIKV) infection. It has also been used as an AMPK α activator to study its protective effect on myocardial cells against oxygen-glucose deprivation-re-oxygenation (OGD/R).

Biochem/physiol Actions

GSK621 is a direct AMPK activator that exhibits anti-leukemic (300 μM; MOLM-14, HL-60, OCI-AML3) and anti-glioma (Effec. conc. 10-100 μM; U87MG and U251MG) activity, while displaying little cytotoxicity toward normal hematopoietic progenitors, primary human astrocytes, or HCN-1a neuronal cells. When administered via intraperitoneal injection, GSK621 (30 mg/kg twice daily) is shown to reduce leukemia growth and significantly extend the survival of mice xenografted with MOLM-14 cells. AMPK activation by GSK621 leads to mTOR inhibition and Tetraspanin 8 (Tspan8) downregulation in glioma cells, while GSK621-induced cytotoxicity in acute myeloid leukemia (AML) cells is the result of synthetic lethality, where co-activation of AMPK and mTORC1 activates the eIF2a signaling pathway, which in turn triggers autophagic cell death.

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable