PI4KIIIα Inhibitor

GSK-A1 is a selective type III phosphatidylinositol 4-kinase PI4KA (PI4KIIIα) inhibitor with a pIC₅₀ of 8.5-9.8. GSK-A1 inhibits PtdIns(4,5)P2 resynthesis with an IC₅₀ of about 3 nM. GSK-A1 potently decreases the levels of PtdIns(4)P with a negligible effect on PtdIns(4,5)P2. GSK-A1 has the potential for anti-hepatitis C virus (HCV) research.

PIK-93 is the first potent, synthetic PI4K (PI4KIIIβ) inhibitor with IC₅₀ of 19 nM, and also inhibits PI3Kγ and PI3Kα with IC₅₀ of 16 nM and 39 nM, respectively.

BF738735 is a phosphatidylinositol 4-kinase III beta (PI4KIIIβ) inhibitor with an IC₅₀ of 5.7 nM.

PI4KIIIbeta-IN-10 is a potent PI4KIIIβ inhibitor with an IC₅₀ of 3.6 nM.

PI4K-IN-1 (compound 44) is a potent PI4KIII inhibitor, with pIC₅₀ values of 9.0 and 6.6 for PI4KIIIα and PI4KIIIβ, respectively. PI4K-IN-1 also inhibits PI3Kα/β/γ/δ, with pIC₅₀ values of 4.0/<3.7/5.0/<4.1, respectively.

PI4KIIIbeta-IN-9 is a potent PI4KIIIβ inhibitor with an IC₅₀ of 7 nM. PI4KIIIbeta-IN-9 also inhibits PI3Kδ and PI3Kγ with IC₅₀s of 152 nM and 1046 nM, respectively.

MI 14 is a selective PI4KIIIβ inhibitor with IC₅₀s of 54 nM, >100 μM, >100 μM for PI4KIIIβ, PI4KIIIα, PI4KIIα, respectively. MI 14 has antiviral activity against HCV 1b, CVB3, HRVM, HVC 2a.

(S)-GSK-F1 (Compound 28) is an inhibitor for type III phosphatidylinositol 4-kinase α (PI4KIIIα). (S)-GSK-F1 inhibits PI4Kα, PI4Kβ, PI4Kγ, PI3Kα, PI3Kβ and PI3Kδ with pIC₅₀ of 8.3, 6.0, 5.6, 5.6, 5.1 and 5.6, respectively. (S)-GSK-F1 exhibits anti-hepatitis C virus (HCV) activity through inhibition of HCV replication. (S)-GSK-F1 exhibits moderate pharmacokinetic characters in rat model.

AZD2836 (A-831) is a 4-aminopyrazolone compound with anti-HCV activity. AZD2836 inhibits the activity of the host cell kinase PI4KIIIα, causing metabolic disorder of the cell membrane component PI4P that is necessary for viral replication. In the HCV subgenomic replicon cell model, the EC₅₀ values of AZD2836 for genotype 1b (Con1 strain) and genotype 1a (Lemon strain) are 270 nM and 550 nM, respectively.

KR-27370 (compound 7f) is an antiviral agent and selective PI4KIIIβ/PI4KIIIα inhibitor (IC₅₀: 3.1 nM/15.8 nM), against hRV, Ke Saatchivirus and other enteroviruses have inhibitory activity.