Telik, Inc.

About: Telik, Inc. is a based out in . It is known for research contribution in the topics: Insulin receptor & Cancer. The organization has 135 authors who have published 110 publications receiving 2261 citations.

Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death.

Abstract: Glutathione transferases (GSTs) are enzymes that catalyze the conjugation of glutathione (GSH) to a variety of electrophilic substances. Their best known role is as cell housekeepers engaged in the detoxification of xenobiotics. Recently, GSTs have also been shown to act as modulators of signal transduction pathways that control cell proliferation and cell death. Their involvement in cancer cell growth and differentiation, and in the development of resistance to anticancer agents, has made them attractive drug targets. This review is focused on the inhibition of GSTs, in particular GSTP1-1, as a potential therapeutic approach for the treatment of cancer and other diseases associated with aberrant cell proliferation.

Decreased insulin receptor (IR) autophosphorylation in fibroblasts from patients with PCOS: effects of serine kinase inhibitors and IR activators.

Abstract: Insulin resistance is characteristic of many patients with polycystic ovary syndrome (PCOS). Several studies have suggested that a decrease in insulin receptor (IR) autophosphorylation is a significant component of this resistance. In this study, we have used a highly sensitive ELISA to measure IR tyrosine phosphorylation in fibroblasts from patients with PCOS and healthy control women. After the stimulation of intact fibroblasts with insulin, IR tyrosine phosphorylation in cells from the PCOS patients was decreased by approximately 40% when compared with controls. However, when IR were first immunocaptured from fibroblasts and then stimulated with insulin, neither basal nor insulin-stimulated IR autophosphorylation was different between the two groups, suggesting that a factor independent of the IR was involved. To examine the role of increased serine kinase activity in decreased IR autophosphorylation in PCOS, fibroblasts from PCOS patients were pretreated with inhibitors of serine kinases before insulin stimulation. Pretreatment with H7, a nonspecific protein kinase inhibitor, completely reversed the decrease in insulin-stimulated IR autophosphorylation. Pretreatment with H89, an inhibitor of protein kinase A, partially reversed this function, whereas pretreatment with Go ¨ 6983, an inhibitor of protein kinase C, was without effect. We next studied the effects of two small molecule activators of the IR tyrosine kinase: TLK16998 and Merck L7. Both TLK16998 and Merck L7 were able to reverse the impaired insulin-stimulated IR autophosphorylation. In summary, a factor(s) extrinsic to the IR cause impaired IR signaling in fibroblasts from patients with PCOS. Reversal of the impaired IR signaling by inhibitors of serine kinase activity suggests that serine kinase-mediated pathways may be involved in the insulin resistance. Moreover, the observation that TLK16998 and Merck L7 improved IR tyrosine phosphorylation in fibroblasts from patients with PCOS suggests that specific pharmacological therapies might be developed to treat the insulin resistance in PCOS. (J Clin Endocrinol Metab 87: 4088 – 4093, 2002)

Method to identify analyte-binding ligands

Abstract: The invention provides methods to obtain panels of low molecular weight polymers resulting from varying constituent monomers, which panels are systematically diverse with respect to two or more variables. The panels can be screened for members (paralogs) which are capable of specifically binding a target moiety. Such paralogs are useful for chromatographic separations and purifications of desired analytes and in binding assays, such as immunoassays, involving said analytes, as well as for any purpose which requires said specific binding. The invention also provides kits for these determinations, and methods to synthesize panels of candidate paralogs and use of these panels to generate analyte profiles and cross reactivity matrices.

Method to produce immunodiagnostic reagents

Abstract: Screening methods to obtain suitable antibodies for use in immunoassays for analytes not ordinarily susceptible to detection by this means involves in vitro screening of panels of cells secreting a representative selection of antibodies. An application of this method also permits the preparation of specific mimotopes which mimic the immunological activity of the desired analyte, which mimotopes can then be used as competitors in the immunoassay or can be used to immunize subject mammals in order to improve the specificity and affinity of the antibodies. Methods to identify a particular analyte by its pattern of binding strength to a panel of related antibodies and to match an arbitrary analyte with an immunoreactive member of a panel of candidate antibodies are also disclosed.