LY2584702 is a potent, highly selective adenosine triphosphate (ATP) competitive inhibitor against p70 S6 kinase, a downstream component of the phosphatidylinositol-3-kinase signalling pathway which regulates cell proliferation and survival. LY2584702 underwent clinical trials against solid tumors both as a monotherapy and in combination with erlotinib or everolimus. No responses were observed for treatment as a single agent. LY2584702 was not well tolerated when administered with erlotinib, therefore this combination is not feasible. The combination with everolimus was better tolerated but yielded very limited clinical benefit.

AT13148, being developed by Astex Pharmaceuticals and its collaborators, is an orally active small molecule inhibitor of Rho activated kinases (ROCK) 1 and 2 and of protein kinase (PK) A and is currently in phase 1 clinical studies under Cancer Research UK’s Clinical Development Program (CDP). AT13148 is currently being tested in a phase 1 clinical trial in patients with advanced solid tumors.

RO-31-8220 is a cell-permeable staurosporine analog, that shows potent inhibition of PKC α, PKC βI, PKC βII, PKC γ, and PKC ε. Ro 31-8220 also inhibits MSK1, MAPKAPK1, RSK, GSK3β, and S6K1 with a potency similar to that for PKC. Ro 31-8220 alters cellular protein kinase C localization and potently inhibits the growth of A549 and MCF-7 cells with IC50 of 0.78 μM and 0.897 μM, respectively. RO 31-8220 enhances epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation. Ro 31-8220 significantly decreases apoE secretion from primary human macrophages by inhibiting vesicular transport of apoE to the plasma membrane without significantly affecting apoE mRNA or apoE protein levels.

RO-31-8220 is a cell-permeable staurosporine analog, that shows potent inhibition of PKC α, PKC βI, PKC βII, PKC γ, and PKC ε. Ro 31-8220 also inhibits MSK1, MAPKAPK1, RSK, GSK3β, and S6K1 with a potency similar to that for PKC. Ro 31-8220 alters cellular protein kinase C localization and potently inhibits the growth of A549 and MCF-7 cells with IC50 of 0.78 μM and 0.897 μM, respectively. RO 31-8220 enhances epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation. Ro 31-8220 significantly decreases apoE secretion from primary human macrophages by inhibiting vesicular transport of apoE to the plasma membrane without significantly affecting apoE mRNA or apoE protein levels.