51339-40-3Relevant articles and documents
SMALL MOLECULE INHIBITORS OF G PROTEIN COUPLED RECEPTOR 6 KINASE POLYPEPTIDES
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Page/Page column 109, (2015/11/10)
This document relates to inhibitors of G protein coupled receptor 6 kinase (GRK6) polypeptides as well as methods and materials for using such inhibitors to treat hematological malignancies, inflammation diseases, and autoimmune disorders.
KINASE INHIBITORS
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Paragraph 0773, (2014/10/16)
There are provided compounds of formula I, wherein R1A to R1E, R2 to R5, L and X1 to X3 have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.
Design, synthesis and in vitro characterization of novel hybrid peptidomimetic inhibitors of STAT3 protein
Shahani, Vijay M.,Yue, Peibin,Fletcher, Steven,Sharmeen, Sumaiya,Sukhai, Mahadeo A.,Luu, Diana P.,Zhang, Xiaolei,Sun, Hong,Zhao, Wei,Schimmer, Aaron D.,Turkson, James,Gunning, Patrick T.
experimental part, p. 1823 - 1838 (2011/04/17)
Aberrant activation of oncogenic signal transducer and activator of transcription 3 (STAT3) protein signaling pathways has been extensively implicated in human cancers. Given STAT3's prominent dysregulatory role in malignant transformation and tumorigenesis, there has been a significant effort to discover STAT3-specific inhibitors as chemical probes for defining the aberrant STAT3-mediated molecular events that support the malignant phenotype. To identify novel, STAT3-selective inhibitors suitable for interrogating STAT3 signaling in tumor cells, we explored the design of hybrid molecules by conjugating a known STAT3 inhibitory peptidomimetic, ISS610 to the high-affinity STAT3-binding peptide motif derived from the ILR/gp-130. Several hybrid molecules were examined in in vitro biophysical and biochemical studies for inhibitory potency against STAT3. Lead inhibitor 14aa was shown to strongly bind to STAT3 (KD = 900 nM), disrupt STAT3:phosphopeptide complexes (Ki = 5 μM) and suppress STAT3 activity in in vitro DNA binding activity/electrophoretic mobility shift assay (EMSA). Moreover, lead STAT3 inhibitor 14aa induced a time-dependent inhibition of constitutive STAT3 activation in v-Src transformed mouse fibroblasts (NIH3T3/v-Src), with 80% suppression of constitutively-active STAT3 at 6 h following treatment of NIH3T3/v-Src. However, STAT3 activity recovered at 24 h after treatment of cells, suggesting potential degradation of the compound. Results further showed a suppression of aberrant STAT3 activity in NIH3T3/v-Src by the treatment with compound 14aa-OH, which is the non-pTyr version of compound 14aa. The effect of compounds 14aa and 14aa-OH are accompanied by a moderate loss of cell viability.
