SML2175

GSK360A

≥98% (HPLC)

• Synonym(s): GSK 1120360A, GSK1120360A, N-[[1-(2-Cyclopropylethyl)-6-fluoro-1,2-dihydro-4-hydroxy-2-oxo-3-quinolinyl]carbonyl]glycine, N-[[1-(2-Cyclopropylethyl)-6-fluoro-4-hydroxy-2-oxo-1,2-dihydro-3-quinolinyl]carbonyl]glycine
• Empirical Formula (Hill Notation): C₁₇H₁₇FN₂O₅
• CAS Number: 931399-19-8
• Molecular Weight: 348.33
• MDL number: MFCD27977959
• UNSPSC Code: 12352200

Properties

• Assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear (warmed)
• storage temp.: 2-8°C
• SMILES string: OC(C1=C(N2CCC3CC3)C=CC(F)=C1)=C(C(NCC(O)=O)=O)C2=O
• InChI: 1S/C17H17FN2O5/c18-10-3-4-12-11(7-10)15(23)14(16(24)19-8-13(21)22)17(25)20(12)6-5-9-1-2-9/h3-4,7,9,23H,1-2,5-6,8H2,(H,19,24)(H,21,22)
• InChI key: TYHRZQVUPPODPT-UHFFFAOYSA-N

Description

Biochem/physiol Actions

GSK360A (GSK1120360A) is an orally active HIF-prolyl 4-hydroxylase (HIF-PHD) inhibitor that targets all three HIF-PHD isoforms (PHD1 > PHD2 = PHD3) with high potency (IC50 from 10-120 nM) in a 2-oxoglutarate (2-OG)-competitive manner. GSK360A promotes cardiomyocyte mitochondrial aerobic glycolysis under normoxic conditions by stabilizing cellular hypoxia-inducible factor-1 (HIF-1) and thereby upregulating HIF-1α target genes transcription (50 μM for 8 hrs in murine cardiomyocyte HL-1 cultures), including pyruvate dehydrogenase kinase-1 (PDK1) and hexokinase II (HKII). GSK360A treatment is shown to protect against acute myocardial ischemia–reperfusion injury (IRI) both in cultures and in rats in vivo (30 mg/kg p.o.) by reducing mitochondrial permeability transition pore (MPTP) opening and oxidative stress during IRI.

Orally active, potent HIF prolyl 4-hydroxylase (PHD) inhibitor with in vitro and in vivo efficacy against acute myocardial ischemia-reperfusion injury (IRI).

Safety Information

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