6H-INDENO[1,2-E]TETRAZOLO[1,5-B][1,2,4]TRIAZIN-6-ONE

Description

KP372-1 is a specific Akt inhibitor that demonstrates at least 10-fold selectivity against a panel of additional kinase targets, including CDK1, ERK1, GSK3β, LCK, MEK1, PKA, PKC, and S6K. By blocking Akt signaling, KP372-1 has been shown to inhibit proliferation and to induce apoptosis of thyroid cancer cells with an IC₅₀ value of 30-60 nM in vitro. In acute myelogenous leukemia cells, KP372-1 is reported to inhibit the kinase activity of Akt, PDK1, and FLT3, decreasing the colony-forming ability of these cells with an IC₅₀ value less than 200 nM.

Uses

KP372-1 is a specific Akt inhibitor that demonstrates at least 10-fold selectivity against a panel of additional kinase targets, including CDK1, ERK1, GSK3β, LCK, MEK1, PKA, PKC, and S6K. By blocking Akt signaling, KP372-1 has been shown to inhibit proliferation and to induce apoptosis of thyroid cancer cells.

in vitro

a previous study found that kp372-1 could block signalling downstream of akt in thyroid tumour cells, resulting in inhibition of cell proliferation and increased apoptosis [1]. another study showed that kp372-1 directly inhibited the kinase activity of akt, flt3, and pdk1concentration-dependently. western blot analyses indicated kp372-1 decreased the phosphorylation of akt on both ser(473) and thr(308). moreover, the treatment of aml cell lines with kp372-1 led to rapid generation of reactive oxygen species and stimulation of oxygen consumption. in addition, kp372-1 was able to induce pronounced apoptosis in aml cell lines and primary samples irrespective of their flt3 status, but not in normal cd34(+) cells [2].

IC 50

30-60 nm for thyroid cancer cells

References

[1] mandal, m. ,kim, s.,younes, m.n., et al. the akt inhibitor kp372-1 suppresses akt activity and cell proliferation and induces apoptosis in thyroid cancer cells. british journal of cancer 92(10), 1899-1905 (2005).
[2] zeng, z. ,samudio, i.j.,zhang, w., et al. simultaneous inhibition of pdk1/akt and fms-like tyrosine kinase 3 signaling by a small-molecule kp372-1 induces mitochondrial dysfunction and apoptosis in acute myelogenous leukemia. cancer research 66(7), 3737-3746 (2006).