PIKfyve Inhibitor

Apilimod (STA 5326) is a potent IL-12/IL-23 inhibitor, and strongly inhibits IL-12 with IC₅₀s of 1 nM and 2 nM, in IFN-γ/SAC-stimulated human PBMCs and SAC-treated monkey PBMCs, respectively. Apilimod is a potent and highly selective PIKfyve inhibitor.

Vacuolin-1 is a potent and cell-permeable lysosomal exocytosis inhibitor. Vacuolin-1 blocks the Ca²⁺-dependent exocytosis of lysosomes and prevents the release of lysosomal content without affecting the process of resealing. vacuolin‐1 is a potent and selective PIKfyve inhibitor and inhibits late‐stage autophagy by impairing lysosomal maturation. Vacuolin-1 can induce vacuole formation and increase the percentage of enucleated cells.

YM-201636 is a potent and selective PIKfyve inhibitor with an IC₅₀ of 33 nM. YM-201636 also inhibits p110α with an IC₅₀ of 3.3 μM. YM-201636 inhibits retroviral replication.

Apilimod (STA 5326) mesylate is a potent IL-12/IL-23 inhibitor, and strongly inhibits IL-12 with IC₅₀s of 1 nM and 2 nM, in IFN-γ/SAC-stimulated human PBMCs and SAC-treated monkey PBMCs, respectively. Apilimod is a potent and highly selective PIKfyve inhibitor.

APY0201 is a potent PIKfyve inhibitor, which inhibits the conversion of PtdIns3P to PtdIns(3,5)P₂ in the presence of in the presence of [³³P]ATP with an IC₅₀ of 5.2 nM. APY0201 also inhibits IL-12/IL-23 production.

MOMIPP, a macropinocytosis inducer, is a PIKfyve inhibitor. MOMIPP penetrates the blood-brain barrier (BBB).

PIKfyve-IN-1 is a highly potent and cell-active chemical probe that inhibits phosphatidylinositol-3phosphate 5-kinase (PIKfyve) with IC₅₀ value of 6.9 nM. PIKfyve-IN-1 can be used for the research of PIKfyve in virology. PIKfyve-IN-1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

DC-SX029 is a potent SNX10 protein-protein interaction (PPI) inhibitor with oral activity with an estimated K_D constant of ~0.935 μM by surface plasmon resonance (SPR). DC-SX029 blocks the SNX10-PIKfyve interaction, thereby decreased the TBK1/c-Rel signaling activation. DC-SX029 does not affect the protein level of SNX10. DC-SX029 has the potential for inflammatory bowel disease (IBD) research.

WX8 (Ro 91-4714) is an ATP-competitive PIKFYVE inhibitor, with K_d values of 0.9 nM and 340 nM for PIKFYVE and PIP4K2C, respectively. WX8 (Ro 91-4714) inhibits lysosomal fission without effecting homotypic lysosomal fusion. WX8 (Ro 91-4714) is used in the research of autophagy-dependent cancer.

RMC-113 is a PIP4K2C and PIKfyve inhibitor with the K_i vaules of 46 nM and 370 nM. RMC-113 reverses SARS-CoV-2-induced impairment of autophagic flux. RMC-113 shows antiviral activity.

PIKfyve-IN-2 is a potent PIKfyve kinase inhibitor and can be used for cancers, autoimmune disorders research.

UNI418 is a dual inhibitor of PIKfyve and PIP5K1C with antiviral activity against SARS-CoV-2 (EC₅₀=1.4 μM). UNI418 blocks ACE2-mediated SARS-CoV-2 viral endocytosis by inhibiting PIP5K1C (IC₅₀=60.1 nM; K_d=61 nM). In addition, UNI418 inhibits the proteolytic activation of proteases regulated by PIKfyve (K_d=0.78 nM) to prevent SARS-CoV-2 from entering host cells.

PIKfyve-IN-4 (Compound 40) is an orally active and selective inhibitor of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve), with an IC₅₀ of 0.60 nM. PIKfyve-IN-4 exhibits good systemic tolerance.

AS2677131 is a potent and orally active PIKfyve inhibitor. AS2677131 inhibits f IL-12p40, IL-6 and IL-1β through a PIKfyve-c-Rel pathway. AS2677131 selectively inhibits DNA-binding activity of c-Rel to IL-12p40 and IL-1β promoter. AS2677131 inhibits MHC class II expression on B cells. AS2677131 can be used for the researches of inflammation and immunology, such as arthritis.

AS2795440 is a PIKfyve inhibitor. AS2795440 selectively inhibits proinflammatory cytokine such as IL-12p40 and IL-6 production and B cell activation without affecting Ca²⁺ signaling. AS2795440 significantly reduces joint inflammation and bone loss in adjuvant-induced arthritis (AIA) mice model. AS2795440 can be used for inflammatory and autoimmune diseases like rheumatoid arthritis, psoriasis and inflammatory bowel disease research.

TMX-4140 is a selective PIP4K2C inhibitor with a K_D of 7.2 nM for PIP4K2C over PIP4K2B. TMX-4140 can be used for synthesis of PROTAC TMX-4153 (HY-153119).