PKG drug G1

• CAT Number: I020232
• CAS Number: 374703-78-3
• Molecular Formula: C13H11N3OS
• Molecular Weight: 257.31
• Purity: ≥95%
• Synonyms: 4-hydroxy-5-[(Z)-(2-methylindol-3-ylidene)methyl]-1,3-dihydroimidazole-2-thione
• InChI: InChI=1S/C13H11N3OS/c1-7-9(6-11-12(17)16-13(18)15-11)8-4-2-3-5-10(8)14-7/h2-6,17H,1H3,(H2,15,16,18)/b9-6+
• InChIKey: BPJCCABLAZZIEJ-RMKNXTFCSA-N
• SMILES: CC1=NC2=CC=CC=C2C1=CC3=C(NC(=S)N3)O

PKG agent G1 targets C42 of PKG Iα. PKG agent G1 can couple to vasodilation and blood pressure lowering by a C42 PKG Iα-independent mechanism.
PKG drug G1 induces vasodilation of isolated resistance blood vessels and blood pressure lowering in a mouse model of angiotensin II–induced hypertension. PKG drug G1 efficiently relaxes WT but not knockin (KI) vessels, which is then assessed in a murine model of hypertension. PKG drug G1 lowers blood pressure in hypertensive WT, but not KI, mice in vivo. PKG drug G1 is tested in vivo in healthy mice implanted with telemetric devices that allow blood pressure and heart rate to be constantly monitored. PKG drug G1 or vehicle control is administrated by intraperitoneal injection, and the acute impact on hemodynamics assessed. PKG drug G1 administered at 7.4 mg/kg does not decrease blood pressure, but there is a concomitant reflex tachycardia. When this is repeated using 14.8 mg/kg dose of PKG drug G1, again blood pressure is not altered-but this higher dose induces a potentiated increase in heart rate[1].

Reference

[1]. Burgoyne JR, et al. Proof of Principle for a Novel Class of Antihypertensives That Target the Oxidative Activation of PKG Iα (Protein Kinase G Iα). Hypertension. 2017 Sep;70(3):577-586.
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