Category: 2222768-84-3

Hayashi, Kumiko; Miyamoto, Miki G.; Niwa, Shinsuke published the artcile< Effects of dynein inhibitor on the number of motor proteins transporting synaptic cargos>, Application In Synthesis of 2222768-84-3, the main research area is dynein inhibitor motor protein synaptic cargo.

Synaptic cargo transport by kinesin and dynein in hippocampal neurons was investigated by noninvasively measuring the transport force based on nonequilibrium statistical mechanics. Although direct phys. measurements such as force measurement using optical tweezers are difficult in an intracellular environment, the noninvasive estimations enabled enumerating force-producing units (FPUs) carrying a cargo comprising the motor proteins generating force. The number of FPUs served as a barometer for stable and long-distance transport by multiple motors, which was then used to quantify the extent of damage to axonal transport by dynarrestin, a dynein inhibitor. We found that dynarrestin decreased the FPU for retrograde transport more than for anterograde transport. This result indicates the applicability of the noninvasive force measurements. In the future, these measurements may be used to quantify damage to axonal transport resulting from neuronal diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases.

Biophysical Journal published new progress about Alzheimer disease. 2222768-84-3 belongs to class thiazole, and the molecular formula is C22H23F2N3O2S, Application In Synthesis of 2222768-84-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Mercadante, Dayna L.; Manning, Amity L.; Olson, Sarah D. published the artcile< Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length>, Synthetic Route of 2222768-84-3, the main research area is cortical dynein bipolar spindle mitosis.

Proper formation and maintenance of the mitotic spindle is required for faithful cell division. Although much work has been done to understand the roles of the key mol. components of the mitotic spindle, identifying the consequences of force perturbations in the spindle remains a challenge. We develop a computational framework accounting for the minimal force requirements of mitotic progression. To reflect early spindle formation, we model microtubule dynamics and interactions with major force-generating motors, excluding chromosome interactions that dominate later in mitosis. We directly integrate our exptl. data to define and validate the model. We then use simulations to analyze individual force components over time and their relationship to spindle dynamics, making it distinct from previously published models. We show through both model predictions and biol. manipulation that rather than achieving and maintaining a constant bipolar spindle length, fluctuations in pole-to-pole distance occur that coincide with microtubule binding and force generation by cortical dynein. Our model further predicts that high dynein activity is required for spindle bipolarity when kinesin-14 (HSET) activity is also high. To the best of our knowledge, our results provide novel insight into the role of cortical dynein in the regulation of spindle bipolarity.

Biophysical Journal published new progress about Cell division. 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

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>, Computed Properties 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, Computed Properties of 2222768-84-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Majstrowicz, Katarzyna; Honnert, Ulrike; Nikolaus, Petra; Schwarz, Vera; Oeding, Stefanie J.; Hemkemeyer, Sandra A.; Baehler, Martin published the artcile< Coordination of mitochondrial and cellular dynamics by the actin-based motor Myo19>, Application of C22H23F2N3O2S, the main research area is actin motor myosin mitochondrial cellular dynamic coordination; Cell adhesion; Mitochondria; Mitosis; Myosin.

Myosin XIX (Myo19) is an actin-based motor that competes with adaptors of microtubule-based motors for binding to the outer mitochondrial transmembrane proteins Miro1 and Miro2 (collectively Miro, also known as RhoT1 and RhoT2, resp.). Here, we investigate which mitochondrial and cellular processes depend on the coordination of Myo19 and microtubule-based motor activities. To this end, we created Myo19-deficient HEK293T cells. Mitochondria in these cells were not properly fragmented at mitosis and were partitioned asym. to daughter cells. Respiratory functions of mitochondria were impaired and ROS generation was enhanced. On a cellular level, cell proliferation, cytokinesis and cell-matrix adhesion were neg. affected. On a mol. level, Myo19 regulates focal adhesions in interphase, and mitochondrial fusion and mitochondrially associated levels of fission protein Drp1 and adaptor proteins dynactin and TRAK1 at prometaphase. These alterations were due to a disturbed coordination of Myo19 and microtubulebased motor activities by Miro.

Journal of Cell Science published new progress about Bacteriophage Miro1. 2222768-84-3 belongs to class thiazole, and the molecular formula is C22H23F2N3O2S, Application of C22H23F2N3O2S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Mercadante, Dayna L.; Manning, Amity L.; Olson, Sarah D. published the artcile< Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length>, Formula: C22H23F2N3O2S, the main research area is cortical dynein bipolar spindle mitosis.

Proper formation and maintenance of the mitotic spindle is required for faithful cell division. Although much work has been done to understand the roles of the key mol. components of the mitotic spindle, identifying the consequences of force perturbations in the spindle remains a challenge. We develop a computational framework accounting for the minimal force requirements of mitotic progression. To reflect early spindle formation, we model microtubule dynamics and interactions with major force-generating motors, excluding chromosome interactions that dominate later in mitosis. We directly integrate our exptl. data to define and validate the model. We then use simulations to analyze individual force components over time and their relationship to spindle dynamics, making it distinct from previously published models. We show through both model predictions and biol. manipulation that rather than achieving and maintaining a constant bipolar spindle length, fluctuations in pole-to-pole distance occur that coincide with microtubule binding and force generation by cortical dynein. Our model further predicts that high dynein activity is required for spindle bipolarity when kinesin-14 (HSET) activity is also high. To the best of our knowledge, our results provide novel insight into the role of cortical dynein in the regulation of spindle bipolarity.

Biophysical Journal published new progress about Cell division. 2222768-84-3 belongs to class thiazole, and the molecular formula is C22H23F2N3O2S, Formula: C22H23F2N3O2S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Majstrowicz, Katarzyna; Honnert, Ulrike; Nikolaus, Petra; Schwarz, Vera; Oeding, Stefanie J.; Hemkemeyer, Sandra A.; Baehler, Martin published the artcile< Coordination of mitochondrial and cellular dynamics by the actin-based motor Myo19>, SDS of cas: 2222768-84-3, the main research area is actin motor myosin mitochondrial cellular dynamic coordination; Cell adhesion; Mitochondria; Mitosis; Myosin.

Myosin XIX (Myo19) is an actin-based motor that competes with adaptors of microtubule-based motors for binding to the outer mitochondrial transmembrane proteins Miro1 and Miro2 (collectively Miro, also known as RhoT1 and RhoT2, resp.). Here, we investigate which mitochondrial and cellular processes depend on the coordination of Myo19 and microtubule-based motor activities. To this end, we created Myo19-deficient HEK293T cells. Mitochondria in these cells were not properly fragmented at mitosis and were partitioned asym. to daughter cells. Respiratory functions of mitochondria were impaired and ROS generation was enhanced. On a cellular level, cell proliferation, cytokinesis and cell-matrix adhesion were neg. affected. On a mol. level, Myo19 regulates focal adhesions in interphase, and mitochondrial fusion and mitochondrially associated levels of fission protein Drp1 and adaptor proteins dynactin and TRAK1 at prometaphase. These alterations were due to a disturbed coordination of Myo19 and microtubulebased motor activities by Miro.

Journal of Cell Science published new progress about Bacteriophage Miro1. 2222768-84-3 belongs to class thiazole, and the molecular formula is C22H23F2N3O2S, SDS of cas: 2222768-84-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

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