PI4K 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.

PI-273 is a first reversibly and specific phosphatidylinositol 4-kinase (PI4KIIα) inhibitor with an IC₅₀ of 0.47 μM. PI-273 can inhibit breast cancer cell proliferation, block the cell cycle and induce cell apoptosis.

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.

Pipinib is an ATP-competitive and selective phosphatidylinositol 4-kinase IIIb (PI4KB) inhibitor with an IC₅₀ of 2.2 μM. Pipinib reduces intracellular PI4P levels. Pipinib inhibits GLI-mediated transcription, the expression of Hedgehog target genes, and blocks the trafficking of Smoothened to cilia. Pipinib can be used in the research of basal cell carcinoma and medulloblastoma.

Echiguanine B is a phosphatidylinositol-4-kinase (PI4K) inhibitor with an IC₅₀ of 0.11 μg/mL against human targets. Echiguanine B inhibits phosphatidylinositol-4-kinase activity in the cell membranes of epithelial cancer cells. Echiguanine B can be used in cancer-related research.

Echiguanine A is a phosphatidylinositol 4-kinase (PI4KIIα) inhibitor with an IC₅₀ of 0.04 μg/mL. Echiguanine A inhibits phosphatidylinositol 4-kinase activity in cell membrane extracts. Echiguanine A is applicable for cancer research.

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.

NC03 is a PI4K2A inhibitor and reducing agent. NC03 inhibits the activity of PI4K2A, thereby reducing the production of PI4P in the cellular compartments where PI4K2A functions. NC03 rapidly induces a decrease in PI4P pools in the Golgi and endosomal compartments. NC03 reduces PI4P production in Rab7-positive late endosomes.

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.

T-00127_HEV1 is a phosphatidylinositol 4-kinase III beta (PI4KB) inhibitor with an IC₅₀ of 60 nM.

GSK-F1 (Compound F1) is an orally active PI4KA inhibitor with pIC₅₀ values of 8.0, 5.9, 5.8, 5.9, 5.9 and 6.4 against PI4KA, PI4KB, PI3KA, PI3KB, PI3KG and PI3KD, respectively. GSK-F1 can be used for HCV infection research.

KDU691, an imidazopyrazine with potent anti-parasitic activity against blood stage schizonts, gametocytes and liver stages, is a Plasmodium PI4K inhibitor. KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites.

MMV390048 is a representative of a new chemical class of Plasmodium PI4K inhibitor (K_d^app=0.3 µM). MMV390048 binds to the ATP binding site of Plasmodium PI4K and does not bind to other P. falciparum and human kinases apart from human PIP4K2C, thus alleviating potential kinase-mediated safety concerns. MMV390048 is an antimalarial agent.

UCB9608 is a potent, selective and orally active PI4KIIIβ inhibitor, with an IC₅₀ of 11 nM, selective over PI3KC2 α, β, and γ lipid kinases. UCB9608 improves metabolic stability and exhibits excellent pharmacokinetic profile, acts as a potent immunosuppressive agent.

PI4KIII beta inhibitor 3 is a novel and high effective PI4KIIIβ inhibitor with IC₅₀ of 5.7 nM.

EDI048 is an orally active, gut-restricted parasiticidal agent. EDI048 specifically binds to the ATP-binding site of Cryptosporidium phosphatidylinositol 4-kinase (CpPI (4) K), blocks parasite membrane biogenesis, arrests the pathogen at the schizont stage, and thus irreversibly clears the infection. EDI048 is rapidly converted to an inactive carboxylic acid metabolite via hepatic first-pass metabolism, with extremely low systemic exposure, good safety profile, and no cardiotoxicity, genotoxicity or off-target effects. EDI048 is used in studies of intestinal cryptosporidiosis in children.

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.

BI-1622 is an orally active, potent and highly selective HER2 (ERBB2) inhibitor, with an IC₅₀ of 7 nM. BI-1622 shows greater than 25-fold selectivity over EGFR. BI-1622 shows high antitumor efficacy in vivo in xenograft mouse tumor models with engineered H2170 and PC9 cells and had a favorable agent metabolism and pharmacokinetics profile.