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| 1 | LKB1 regulated pathways in lung cancer invasion and metastasis显示文摘 | Marcus AI Zhou W | 2010 | J Thorac Oncol2010，5，12： | 1 |
| 2 | Mitotic kinesin inhibitors induce mitotic arrest and cell death in Taxol-resistant and -sensitive cancer cells显示文摘 | Marcus AI Peters U Thomas SL | 2005 | Biol Chem2005，280，11： | 1 |
| 3 | Diagnoss and manage ment of childhood obstructive sleep apnea syndrome 显示文摘 | Marcus C L Brooks L J Draper K A et ai | 2012 | Pedi atries2012，130，3： | 1 |
| 4 | Site-directed deuteration of dronedarone preserves cytochrome P4502J2 activity and mitigates its cardiac adverse effects in canine arrhythmic hearts显示文摘Cytochrome P4502J2(CYP2J2)metabolizes arachidonic acid(AA)to cardioprotective epoxyeicosatrienoic acids(EETs).Dronedarone,an antiarrhythmic drug prescribed for treatment of atrial fibrillation(AF)induces cardiac adverse effects(AEs)with poorly understood mechanisms.We previously demonstrated that dronedarone inactivates CYP2J2 potently and irreversibly,disrupts AA-EET pathway leading to cardiac mitochondrial toxicity rescuable via EET enrichment.In this study,we investigated if mitigation of CYP2J2 inhibition prevents dronedarone-induced cardiac AEs.We first synthesized a deuterated analogue of dronedarone(termed poyendarone)and demonstrated that it neither inactivates CYP2J2,disrupts AA-EETs metabolism nor causes cardiac mitochondrial toxicity in vitro.Our patch-clamp experiments demonstrated that pharmacoelectrophysiology of dronedarone is unaffected by deuteration.Next,we show that dronedarone treatment or CYP2J2 knockdown in spontaneously beating cardiomyocytes indicative of depleted CYP2J2 activity exacerbates beat-to-beat(BTB)variability reflective of proarrhythmic phenotype.In contrast,poyendarone treatment yields significantly lower BTB variability compared to dronedarone in cardiomyocytes indicative of preserved CYP2J2 activity.Importantly,poyendarone and dronedarone display similar antiarrhythmic properties in the canine model of persistent AF,while poyendarone substantially reduces beat-to-beat variability of repolarization duration suggestive of diminished proarrhythmic risk.Our findings prove that deuteration of dronedarone prevents CYP2J2 inactivation and mitigates dronedarone-induced cardiac AEs. | Aneesh V.Karkhanis Gopalakrishnan Venkatesan Ryuichi Kambayashi Jacqueline Wen Hui Leow Marcus Qingrui Han Hiroko Izumi-Nakaseko Ai Goto Jeremy Kah Sheng Pang Boon Seng Soh Pipin Kojodjojo Atsushi Sugiyama Eric Chun Yong Chan | 2022 | Acta Pharmaceutica Sinica B2022，12，10： | 1 |
| 5 | Mitotic kinesin inhibitors induce mitotic arrest and celt death in Taxol-resistant and-sensitive cancer cells 显示文摘 | Marcus AI Peters U Thomas SL | 2005 | J Biol Chem2005，280，11： | 1 |
| 6 | Imaging and tracking of tat peptide-conjugated quantum dots in living cells: New in- sights into nanoparticle uptake, intracellular transport, and vesi- cle shedding显示文摘 | Ruan G Agrawal A Marcus AI | 2007 | J Am Chem Sco2007，129，14： | 1 |
| 7 | Consumer attitudes and use ofantibiotics 显示文摘 | VandenEng J Marcus R Hadler JL et ai | 2003 | Emerg Infect Dis2003，，9： | 1 |
| 8 | The synergistic eombination of the famesyl transferase inhibitor lonafarnib and paclitaxel enhances tu- bulin acetylation and requires a functional tubulin deacetylase 显示文摘 | Marcus AI Zhou J O' Brate A | 2005 | Cancer Res2005，65，9： | 1 |
| 9 | Imaging and tracking of tat peptide-conjugated quantum dots in living cells:new insights into nanoparticle uptake,intracellular transport,and vesicle shedding显示文摘 | Ruan G Agrawal A Marcus AI | 2007 | J Am Chem Soc2007，129，14： | 1 |
| 10 | Recent Earth ob- lateness variations: Unraveling climate and postglaciaI re- bound effects显示文摘 | Dickey J O Marcus S L Viron O D et aI | 2002 | Science2002，298，： | 1 |
| 11 | Imaging and tracking of tat - poptide - conjugated quantum dots in living cells : new insights into nanoparticle uptake, intracellular transport, and vesicle shedding 显示文摘 | Ruan G AgrawalA Marcus AI | 2007 | J AM Chem See2007，129，14： | 1 |
| 12 | Arl2 and Arl3 regulate different microtubule -dependent processes显示文摘 | ZHOU C Cunningham L Marcus AI | 2006 | Mol Biol Cell2006，17，5： | 1 |
| 13 | Modulation of choroidal neovascularization by subrelinal injection of retinal pigment epithelium and polystyrene microbeads 显示文摘 | Schmack I Berglin L Nie X Wen J Kang SJ Marcus AI | 2009 | Mol Vis2009，15，： | 1 |
| 14 | Imaging and tracking of tat-poptide-conjugated quantum dots in living cells:new insights into nanoparticle uptake, intrace显示文摘 | Ruan G Agrawal A Marcus AI | 2007 | J Am Chem Soc2007，129，14： | 1 |
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