A-674563 is a potent, orally available Akt1 inhibitor with an IC50 value of 11nM. Also displays activity against PKA and CDK2 with IC50 values of 16nM and 46nM respectively. A-674563 dose-dependently inhibited survival and proliferation of U937 AML cells and six lines of human AML progenitor cells, yet sparing human peripheral blood mononuclear leukocytes (PBMCs). A-674563 activated caspase-3/9 and apoptosis in the AML cells. intraperitoneal injection of A-674563 at well-tolerated doses suppressed U937 leukemic xenograft tumor growth in nude mice, whiling significantly improving the animal survival. A-674563 exerts potent anti-leukemic activity in vitro and in vivo, possibly via concurrent targeting Akt and SphK1 signalings. A-674563 also exerts potent anti-melanoma activity, involving Akt-dependent and Akt-independent mechanisms.

PHA-690509 is an ATP-competitive CDK inhibitor developed at Nerviano Medical Sciences. PHA-690509 demonstrates antiviral activity against ZIKV.

NU6102 is a potent CDK1/cyclin B and CDK2/cyclin A3 inhibitor (IC50 values are 9.5 and 5.4 nM for CDK1/cyclin B and CDK2/cyclin A3 respectively). Antiproliferative agent. Induces G2/M cell cycle arrest. Shows antitumor effects in vivo. NU6102 and its prodrug NU6301 have pharmacological properties consistent with CDK2 inhibition, and represent useful tool molecules for the evaluation of CDK2 as a target in cancer.

Corydine is a naturally occurring compound which can be extracted from plants such as Chelidonium majus, Corydalis marschalliana, C. bulbosa, C slivenensis, Glaucium grandiflorum. Corydine has shown some efficacy as an anti-cancer compound in several cell models and was examined along with related compounds from Stephania dinklagei for antiprotozoal activities. (+)- and (-)- Corydine were tested as neuromuscular blocking agents were it was found that there was a modest preference for (+)-corydine.

AZD-5597 is potent imidazole pyrimidine amide CDK inhibitor with in vitro anti-proliferative effects against a range of cancer cell lines. AZD-5597 exhibited excellent aqueous solubility, photostability, hydrolytic stability, plasma stability and the lack of CYP inhibition. In nude mice implanted subcutaneously with SW620 human colon adenocarcinoma cells, AZD-5597 (15 mg/kg, dosed intermittently for 3 weeks, ip) inhibited tumor volume by 55%. The overall profile of AZD-5597 indicated that it was suitable for further development as an iv agent.

Olomoucine acts as a competitive inhibitor of ATP in cyclin-dependent kinase 1/2/5, and mitogen-activated protein kinase 1. Olomoucine is an anti-mitotic compound that induces cell death preferentially in cancer cell lines, but also at a slower rate in non-cancer cells. It has been studied pre-clinically in a number of cancer models but has not been reported in any human trials. Olomoucine has also seen some preliminary investigation in mouse models of Herpes Simplex Viral Encephalitis.

Fluspirilene, a neuroleptic drug, which is used clinically to treat schizophrenic patients, by blocking of dopamine receptors, especially the dopamine D2 receptors. Fluspirilene also displays calcium channel-blocking activity; it inhibits glutamate release primarily by reducing presynaptic Ca2+ influx via N-type Ca2+ channels that also may contribute to the antischizophrenic action of the drug. Recently in the frame of a project of drugs repositioning, fluspirilene was studied as an anti-cancer drug. It was found, that fluspirilene demonstrates a significant inhibitory effect on the proliferation and invasion of glioma cells. Thus, it can be a promising drug for the treatment of glioblastoma. In addition, fluspirilene, as a potential cyclin-dependent kinase 2 inhibitor, was investigated in animal models for the treatment of human hepatocellular carcinoma. Taken into account that fluspirilene has a long history of safe human use, the drug can be applicable in clinical therapy for cancer’s disease immediately.

RGB-286638 is a multi-targeted protein kinase inhibitor currently in Phase 1 clinical testing. In vitro cell-free kinase assays indicated that RGB-286638 inhibits CDK1, 2, 3, 4, 5, and 9 and is less active against CDK6 and 7. The RGB-286638 compound has been shown to inhibit the processes controlling cell division in cancer cells by targeting multiple cyclin-dependent kinase proteins involved in regulating the cell cycle. RGB-286638 has also been shown to induce apoptosis (programmed cell death) and to inhibit other important protein kinases involved in the proliferation of cancer cells. RGB-286638 treatment results in tumor regression and increased survival in a number of pre-clinical models of solid and hematological tumors.