KU-60019 is a selective ATM kinase inhibitor. ATM is an ataxia telangiectasia (A-T) mutated, which plays a critical role in cell cycle checkpoints and DNA repair. Thus, specific small molecule inhibitors targeting ATM could perhaps be developed into efficient radiosensitizers. KU-60019 was a highly effective radiosensitizer of human glioma cells. A-T fibroblasts were not radiosensitized by KU-60019 and were suggested that the ATM kinase was specifically targeted. In xenograft models was shown, that the combination of KU-60019 and radiation significantly increased survival of mice than KU-60019 alone, radiation alone, or no treatment. In addition, p53-mutant gliomas were much more sensitive to KU-60019 radiosensitization than wild-type glioma.

ORM-15341 is an active main metabolite of ODM-201, which is structurally distinct from any known antiandrogens including the second-generation antiandrogens enzalutamide. ORM-15341 is a potent and full antagonist for human androgen receptor. It was shown, that in VCaP prostate cancer cells containing endogenous AR gene amplification and overexpressing AR, ORM-15341 inhibited cell proliferation more efficiently than enzalutamide or ARN-509.

CB1-IN-1 is a peripas a peripherally restricted CB1R antagonist. It cause weight-loss in diet-induced obese mice.

3',5'-DICHLORO-2-HYDROXY-2-METHYLBUT-3-ENANILIDE is a metabolite of vinclozolin, a dicarboximide fungicide widely used in the United States and Europe for control of diseases caused by B. cineera, S. sclerotiorum, and Monilinia species in fruits, grapes, ornamental plants, turfgrass and vegetables. This fungicide possesses antiandrogenic activity. 3',5'-DICHLORO-2-HYDROXY-2-METHYLBUT-3-ENANILIDE has an antiandrogenic activity too. Moreover, it is an antagonist of progesterone, glucocorticoid, mineralocorticoid receptors and agonist for both estrogen receptors. This ability to act via more than one mechanism must be taken into consideration in the risk assessment process.

BMS-378806 is a recently discovered small molecule HIV-1 inhibitor that blocks viral entrance to cells. The compound exhibits potent inhibitory activity against a panel of R5-(virus using the CCR5 coreceptor), X4-(virus using the CXCR4 coreceptor), and R5/X4 HIV-1 laboratory and clinical isolates of the B subtype (median EC50 of 0.04 microM) in culture assays. BMS-378806 is selective for HIV-1 and inactive against HIV-2, SIV and a panel of other viruses, and exhibits no significant cytotoxicity in the 14 cell types tested (concentration for 50% reduction of cell growth, >225 microM). BMS-378806 was proved to be specific for HIV-1, with no activity against HIV-2 or simian immunodeficiency virus. BMS-378806 is active against HIV-1 isolates irrespective of chemokine receptor preference. Mechanism of action studies demonstrated that BMS-378806 binds to gp120 and inhibits the interactions of the HIV-1 envelope protein to cellular CD4 receptors. BMS-378806 potently inhibited HIV-1 infection regardless of the particular chemokine receptor used.

BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. BMS-345541 was identified as a selective inhibitor of the catalytic subunits of IKK (IKK-2 IC(50) = 0.3 uM, IKK-1 IC(50) = 4 uM). A binding model is proposed in which BMS-345541 binds to similar allosteric sites on IKK-1 and IKK-2, which then affects the active sites of the subunits differently. BMS-345541 was shown to have excellent pharmacokinetics in mice, and peroral administration showed the compound to dose-dependently inhibit the production of serum tumor necrosis factor alpha following intraperitoneal challenge with lipopolysaccharide. BMS-345541 is effective against NF-kappa B activation in mice and represents an important tool for investigating the role of IKK in disease models. BMS-345541 blocks both joint inflammation and destruction in collagen-induced arthritis in mice.

Valinomycin is an ionophore and acts by creating an influx of K+ ions in bacterial cells. It is an antibiotic substance with wide range of activity against different bacteria, fungies and virus-infected cells. Also it demonstrates insecticide and nematocide properties. Because of its toxicity to eukaryotic cells, valinomycin cannot be used in human therapy.

Wortmannin is a fungal metabolite that so far has been shown to act as a selective inhibitor of phosphoinositide 3-kinase. Wortmannin inhibits cancer cell growth and has shown activity against mouse and human tumor xenografts in mice. Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Also blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays.

Conduritol B epoxide is an inhibitor of mammalian glucocerebrosidase and lowers glucosylceramide degradation. Glucosylceramide is the precursor for all of the more complex glycosphingolipids. The experiments on animals were shown, that conduritol B epoxide preserved ganglioside distribution at the neuromuscular junction, delayed disease onset, improved motor function and preserved motor neurons as well as neuromuscular junctions from degeneration. In addition, conduritol B epoxide mitigated gene dysregulation in the spinal cord and restored the expression of genes involved in signal transduction and axonal elongation.

CGP-74588 (Norimatinib, N-Desmethyl Imatinib) is a metabolite of Imatinib, a tyrosine kinase inhibitor, displaying specificity for BCR-ABL. CGP-74588 is pharmacologically active, and shows a similar potency and selectivity profile as the parent drug