Hoeing, Susanne; Yeh, Ting-Yu; Baumann, Matthias; Martinez, Nancy E.; Habenberger, Peter; Kremer, Lea; Drexler, Hannes C. A.; Kuechler, Philipp; Reinhardt, Peter; Choidas, Axel; Zischinsky, Mia-Lisa; Zischinsky, Gunther; Nandini, Swaran; Ledray, Aaron P.; Ketcham, Stephanie A.; Reinhardt, Lydia; Abo-Rady, Masin; Glatza, Michael; King, Stephen J.; Nussbaumer, Peter; Ziegler, Slava; Klebl, Bert; Schroer, Trina A.; Schoeler, Hans R.; Waldmann, Herbert; Sterneckert, Jared published the artcile< Dynarrestin, a Novel Inhibitor of Cytoplasmic Dynein>, Synthetic Route of 2222768-84-3, the main research area is esophageal squamous cell carcinoma proliferation cytoplasmic dynein dynarrestin; ciliary transport; ciliobrevin; dynein; glioblastoma; hedgehog; intraflagellar transport; phenotypic screening; stem cell-based phenotypic screening; vismodegib.
Aberrant hedgehog (Hh) signaling contributes to the pathogenesis of multiple cancers. Available inhibitors target Smoothened (Smo), which can acquire mutations causing drug resistance. Thus, compounds that inhibit Hh signaling downstream of Smo are urgently needed. We identified dynarrestin, a novel inhibitor of cytoplasmic dyneins 1 and 2. Dynarrestin acts reversibly to inhibit cytoplasmic dynein 1-dependent microtubule binding and motility in vitro without affecting ATP hydrolysis. It rapidly and reversibly inhibits endosome movement in living cells and perturbs mitosis by inducing spindle misorientation and pseudoprometaphase delay. Dynarrestin reversibly inhibits cytoplasmic dynein 2-dependent intraflagellar transport (IFT) of the cargo IFT88 and flux of Smo within cilia without interfering with ciliogenesis and suppresses Hh-dependent proliferation of neuronal precursors and tumor cells. As such, dynarrestin is a valuable tool for probing cytoplasmic dynein-dependent cellular processes and a promising compound for medicinal chem. programs aimed at development of anti-cancer drugs.
Cell Chemical Biology published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (GLI1). 2222768-84-3 belongs to class thiazole, and the molecular formula is C22H23F2N3O2S, Synthetic Route of 2222768-84-3.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica