ADA-07

ADA-07 is a TOPK inhibitor with activity at the ATP-binding pocket that does not inhibit MEK1 activity. ADA-07 suppresses solar ultraviolet (SUV)-induced phosphorylation of ERK1/2, p38, and JNKs, and inhibits AP-1 activity. ADA-07 attenuates tumor incidence, multiplicity, and volume in SUV-exposed SKH-1 hairless mice. ADA-07 can be used for the research of solar ultraviolet-induced skin carcinogenesis^[1]. In Vitro:ADA-07 binds directly to the ATP-binding pocket of TOPK via hydrogen bonding with Gly118 and Gly119^[1].
ADA-07 binds TOPK in an ATP-competitive manner^[1].
ADA-07 (2.5 mg; overnight) binds to endogenous TOPK and MEK1/2 present in HaCaT human skin keratinocyte lysates^[1].
ADA-07 (0.5-5 μM; 30 min) potently and selectively inhibits the kinase activity of active human recombinant TOPK, but does not inhibit active human recombinant MEK1^[1].
ADA-07 (1.25-10 μM; 24-48 h) is non-cytotoxic to JB6 P+ mouse epidermal cells and NHDF normal human dermal fibroblasts at concentrations below 10 μM after 24 or 48 h of incubation^[1].
ADA-07 (1.25-5 μM; 4 h pre-incubation) dose-dependently inhibits SUV-induced phosphorylation of ERK1/2, p38, JNKs, and c-Jun in HaCaT human skin keratinocytes and JB6 P+ mouse epidermal cells^[1].
ADA-07 (1.25-5 μM; 24 h) dose-dependently inhibits basal phosphorylation of ERK1/2, p38, JNKs, and c-Jun in SCC12 human squamous cell carcinoma cells and A431 human epidermoid carcinoma cells^[1].
ADA-07 (1.25-5 μM; 1 h pre-incubation) dose-dependently inhibits SUV-induced AP-1 transactivation in JB6 P+ mouse epidermal cells stably expressing an AP-1 luciferase reporter^[1].
ADA-07 (1.25-10 μM; 1-2 weeks) dose-dependently inhibits EGF-induced neoplastic transformation of JB6 P+ mouse epidermal cells in an anchorage-independent growth assay^[1].
ADA-07 (0.625-10 μM; several days) dose-dependently suppresses the proliferation of SCC12 human squamous cell carcinoma cells and A431 human epidermoid carcinoma cells in a crystal violet staining assay^[1].
ADA-07 (1.25-5 μM; 24 h) suppresses AP-1 activity in control A431 human epidermoid carcinoma cells in a dose-dependent manner, but has minimal effect on AP-1 activity in TOPK-knockdown A431 cells, confirming that ADA-07 acts by targeting TOPK^[1]. In Vivo:ADA-07 (0.1-1 mg; topical; 3 times weekly; 28 weeks) completely prevents SUV-induced skin carcinogenesis in SKH-1 hairless mice by inhibiting SUV-induced phosphorylation of ERK1/2, p38, and JNKs and reducing cell proliferation^[1].
ADA-07 (0.1-1 mg; topical; 3 times weekly; 13 weeks) significantly suppresses established SUV-induced skin carcinogenesis in SKH-1 hairless mice by inhibiting SUV-induced phosphorylation of ERK1/2, p38, and JNKs and reducing cell proliferation^[1].