IPK Superfamily Inhibitor

UNC7467 is a potent IP6K inhibitor with values of 4.9, 8.9 and 1320 nM for IP6K2, IP6K1 and IP6K6, respectively. UNC7467 reduces levels of inositol pyrophosphates. UNC7467 can be used for obesity research.

TNP is a competitive, reversible inhibitor of IP6K1 and IP3K, with IC₅₀s of 0.55 μM and 10.2 μM for IP6K1 and IP3K, respectively. TNP competitively binds to the ATP binding site of IP6K, inhibits the generation of 5-IP7, and thus relieves the inhibition of 5-IP7 on the AKT signaling pathway. TNP can enhance insulin sensitivity and promote thermogenesis in adipose tissue. TNP cannot effectively pass through the blood-brain barrier and is mainly used in the study of obesity, type 2 diabetes, and metabolic syndrome. However, TNP also inhibits CYP3A4 and may need further optimization[1][2][3].

LI-2242 is an inositol hexakisphosphate kinase (IP6K) inhibitor. LI-2242 has inhibition effect for IP6K1, IP6K2, IP6K3 and IPMK with IC₅₀ values of 31 nM, 42 nM, 8.7 nM and 1944 nM, respectively. LI-2242 can be used for thew research of type II diabetes, obesity, metabolic complications, venous thrombosis, and psychiatric disorders.

UNC7437 is a inositol phosphate multikinase (IPMK) inhibitor, with an IC₅₀ value of 26.2 nM. UNC7437 exhibits anti-proliferative activity against glioblastoma cells. UNC7437 decreases the accumulation of InsP₄, InsP₅, and InsP₆ in cells. UNC7437 can be used for the study of TEN-negative glioblastoma models.

IP6K-IN-2 is an inositol hexakisphosphate kinase (IP6K1) inhibitor that inhibits IP6K1 enzyme activity with an IC₅₀ value of 110 nM. IP6K-IN-2 can be used for the research of neurological disease and CNS disorders.

IP6K2-IN-1 is a selective flavonoid-based IP6K2 inhibitor with an IC₅₀ value of 0.55 μM. IP6K2-IN-1 shows higher inhibitory potency against IP6K2 than IP6K1 and IP6K3. IP6K2-IN-1 can be utilised as a hit compound for further structural modifications of IP6K2 inhibitors.

SC-919 is an orally active IP6K inhibitor, with an IC₅₀ of < 5.2 nM against IP6K1, < 3.8 nM against IP6K2, and 0.65 nM against IP6K3. By inhibiting the activity of IP6K, SC-919 reduces intracellular IP7 levels, thereby suppressing XPR1-mediated cellular phosphate efflux. SC-919 increases intracellular phosphate and ATP levels while reducing phosphate entry into the bloodstream, thus decreasing plasma phosphate levels. SC-919 can be used in research related to chronic kidney disease and hyperphosphatemia.

IP6K-IN-1 (compound 24) is a potent and selective inhibitor of IP6K with an IC₅₀ of 0.896 μM. IP6K-IN-1 can used in study metabolic disease.

IP6K2-IN-2 (Compound 6) is an IP6K2 inhibitor, with IC₅₀ values of 0.58 μM (IP6K2), 0.86 μM (IP6K1) and 3.08 μM (IP6K3). IP6K2-IN-2 can be used in research of obesity.

IP6K-IN-2 (compound 29c) is an orally bioavailable and blood-brain barrier permeable IP6K inhibitor (IC₅₀: 15.8 nM) that can be used in the study of central nervous system diseases.

UNC9750 is an inositol phosphate multikinase (IPMK) inhibitor with IC₅₀ values ​​of 31.6 and 374 nM for IPMK and IP6K2, respectively.. UNC9750 inhibits cellular accumulation of InsP₅, the direct product of IPMK kinase activity, while having no effect on either InsP6 or InsP₇ levels. UNC9750 has ≥ 75% inhibition of four kinases (DAPK1, DYRK1B, PDGFR, and KDR). UNC9750 can be used for the study of glioblastoma.