Protein kinases represent a very pharmacologically attractive class of targets; however, some members of the family still remain rather unexplored. The biology and therapeutic potential of cdc-like kinases (CLKs) have been explored mainly over the last decade and the first CLK inhibitor, compound SM08502, entered clinical trials only recently. This review summarizes the biological roles and therapeutic potential of CLKs and their heretofore published small-molecule inhibitors, with a focus on the compounds' potential to be utilized as quality chemical biology probes.
- MeSH
- antitumorózní látky farmakologie terapeutické užití MeSH
- inhibitory proteinkinas farmakologie terapeutické užití MeSH
- karcinogeneze účinky léků metabolismus MeSH
- lidé MeSH
- protein-serin-threoninkinasy antagonisté a inhibitory chemie genetika metabolismus MeSH
- tyrosinkinasy antagonisté a inhibitory chemie genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The compound originally known as TIC10 or ONC201 is a new anticancer drug developed by Oncoceutics, Inc. The agent's Investigational New Drug Application for phase I/II clinical studies has been recently approved by Food & Drug Administration. However, a Scripp Institute's group revealed that the compound structure given in all documents, including patents, was erroneous and applied for a patent protection for the correct structure. Chemistry backgrounds associated with this case is reviewed together with the relevant consequences regarding the intellectual property issue.
- Klíčová slova
- bosutinib,
- MeSH
- antitumorózní látky farmakokinetika chemie zásobování a distribuce MeSH
- apoptóza MeSH
- chemické techniky analytické metody využití MeSH
- duševní vlastnictví * MeSH
- farmaceutická technologie MeSH
- isomerie * MeSH
- krystalografie rentgenová MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- příprava léků MeSH
- protein TRAIL MeSH
- tyrosinkinasy * antagonisté a inhibitory chemie MeSH
- Check Tag
- lidé MeSH
Formation of the immunological synapse between an antigen-presenting cell (APC) and a T cell leads to signal generation in both cells involved. In T cells, the lipid raft-associated transmembrane adaptor protein LAT plays a central role. Its phosphorylation is a crucial step in signal propagation, including the calcium response and mitogen-activated protein kinase activation, and largely depends on its association with the SLP76 adaptor protein. Here we report the discovery of a new palmitoylated transmembrane adaptor protein, termed SCIMP. SCIMP is expressed in B cells and other professional APCs and is localized in the immunological synapse due to its association with tetraspanin-enriched microdomains. In B cells, it is constitutively associated with Lyn kinase and becomes tyrosine phosphorylated after major histocompatibility complex type II (MHC-II) stimulation. When phosphorylated, SCIMP binds to the SLP65 adaptor protein and also to the inhibitory kinase Csk. While the association with SLP65 initiates the downstream signaling cascades, Csk binding functions as a negative regulatory loop. The results suggest that SCIMP is involved in signal transduction after MHC-II stimulation and therefore serves as a regulator of antigen presentation and other APC functions.
- MeSH
- adaptorové proteiny signální transdukční chemie metabolismus MeSH
- aktivace lymfocytů MeSH
- antigen prezentující buňky imunologie MeSH
- B-lymfocyty imunologie metabolismus MeSH
- fosfoproteiny metabolismus MeSH
- HEK293 buňky MeSH
- histokompatibilita - antigeny třídy II imunologie metabolismus MeSH
- imunologické synapse chemie MeSH
- lidé MeSH
- malá interferující RNA MeSH
- membránové mikrodomény chemie metabolismus MeSH
- membránové proteiny chemie genetika imunologie metabolismus MeSH
- mitogenem aktivované proteinkinasy metabolismus MeSH
- molekulární sekvence - údaje MeSH
- prezentace antigenu MeSH
- RNA interference MeSH
- sekvence aminokyselin MeSH
- signální transdukce MeSH
- skupina kinas odvozených od src-genu metabolismus MeSH
- src homologní domény MeSH
- T-lymfocyty imunologie MeSH
- tyrosinkinasy chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- fosfoproteiny fyziologie genetika chemie MeSH
- tyrosinkinasy fyziologie chemie MeSH
- Publikační typ
- kongresy MeSH
