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Utilizing structure based drug design and metabolic soft spot identification to optimize the in vitro potency and in vivo pharmacokinetic properties leading to the discovery of novel reversible Bruton's tyrosine kinase inhibitors.
Hopkins BT, Bame E, Bell N, Bohnert T, Bowden-Verhoek JK, Bui M, Cancilla MT, Conlon P, Cullen P, Erlanson DA, Fan J, Fuchs-Knotts T, Hansen S, Heumann S, Jenkins TJ, Gua C, Liu Y, Liu Y, Lulla M, Marcotte D, Marx I, McDowell B, Mertsching E, Negrou E, Romanowski MJ, Scott D, Silvian L, Yang W, Zhong M. Hopkins BT, et al. Among authors: cullen p. Bioorg Med Chem. 2021 Aug 15;44:116275. doi: 10.1016/j.bmc.2021.116275. Epub 2021 Jun 15. Bioorg Med Chem. 2021. PMID: 34314938
Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases.
Marcotte DJ, Liu YT, Arduini RM, Hession CA, Miatkowski K, Wildes CP, Cullen PF, Hong V, Hopkins BT, Mertsching E, Jenkins TJ, Romanowski MJ, Baker DP, Silvian LF. Marcotte DJ, et al. Among authors: cullen pf. Protein Sci. 2010 Mar;19(3):429-39. doi: 10.1002/pro.321. Protein Sci. 2010. PMID: 20052711 Free PMC article.
Optimization of novel reversible Bruton's tyrosine kinase inhibitors identified using Tethering-fragment-based screens.
Hopkins BT, Bame E, Bell N, Bohnert T, Bowden-Verhoek JK, Bui M, Cancilla MT, Conlon P, Cullen P, Erlanson DA, Fan J, Fuchs-Knotts T, Hansen S, Heumann S, Jenkins TJ, Marcotte D, McDowell B, Mertsching E, Negrou E, Otipoby KL, Poreci U, Romanowski MJ, Scott D, Silvian L, Yang W, Zhong M. Hopkins BT, et al. Among authors: cullen p. Bioorg Med Chem. 2019 Jul 1;27(13):2905-2913. doi: 10.1016/j.bmc.2019.05.021. Epub 2019 May 14. Bioorg Med Chem. 2019. PMID: 31138459
Next-generation Bruton's tyrosine kinase inhibitor BIIB091 selectively and potently inhibits B cell and Fc receptor signaling and downstream functions in B cells and myeloid cells.
Bame E, Tang H, Burns JC, Arefayene M, Michelsen K, Ma B, Marx I, Prince R, Roach AM, Poreci U, Donaldson D, Cullen P, Casey F, Zhu J, Carlile TM, Sangurdekar D, Zhang B, Trapa P, Santoro J, Muragan P, Pellerin A, Rubino S, Gianni D, Bajrami B, Peng X, Coppell A, Riester K, Belachew S, Mehta D, Palte M, Hopkins BT, Scaramozza M, Franchimont N, Mingueneau M. Bame E, et al. Among authors: cullen p. Clin Transl Immunology. 2021 Jun 14;10(6):e1295. doi: 10.1002/cti2.1295. eCollection 2021. Clin Transl Immunology. 2021. PMID: 34141433 Free PMC article.
Discovery of structural diverse reversible BTK inhibitors utilized to develop a novel in vivo CD69 and CD86 PK/PD mouse model.
Vandeveer GH, Arduini RM, Baker DP, Barry K, Bohnert T, Bowden-Verhoek JK, Conlon P, Cullen PF, Guan B, Jenkins TJ, Liao SY, Lin L, Liu YT, Marcotte D, Mertsching E, Metrick CM, Negrou E, Powell N, Scott D, Silvian LF, Hopkins BT. Vandeveer GH, et al. Among authors: cullen pf. Bioorg Med Chem Lett. 2023 Jan 15;80:129108. doi: 10.1016/j.bmcl.2022.129108. Epub 2022 Dec 17. Bioorg Med Chem Lett. 2023. PMID: 36538993
A kinase-focused compound collection: compilation and screening strategy.
Sun D, Chuaqui C, Deng Z, Bowes S, Chin D, Singh J, Cullen P, Hankins G, Lee WC, Donnelly J, Friedman J, Josiah S. Sun D, et al. Among authors: cullen p. Chem Biol Drug Des. 2006 Jun;67(6):385-94. doi: 10.1111/j.1747-0285.2006.00396.x. Chem Biol Drug Des. 2006. PMID: 16882313
MOG autoantibodies trigger a tightly-controlled FcR and BTK-driven microglia proliferative response.
Pellerin K, Rubino SJ, Burns JC, Smith BA, McCarl CA, Zhu J, Jandreski L, Cullen P, Carlile TM, Li A, Rebollar JV, Sybulski J, Reynolds TL, Zhang B, Basile R, Tang H, Harp CP, Pellerin A, Silbereis J, Franchimont N, Cahir-McFarland E, Ransohoff RM, Cameron TO, Mingueneau M. Pellerin K, et al. Among authors: cullen p. Brain. 2021 Sep 4;144(8):2361-2374. doi: 10.1093/brain/awab231. Brain. 2021. PMID: 34145876
Organotypic Brain Slice Culture Microglia Exhibit Molecular Similarity to Acutely-Isolated Adult Microglia and Provide a Platform to Study Neuroinflammation.
Delbridge ARD, Huh D, Brickelmaier M, Burns JC, Roberts C, Challa R, Raymond N, Cullen P, Carlile TM, Ennis KA, Liu M, Sun C, Allaire NE, Foos M, Tsai HH, Franchimont N, Ransohoff RM, Butts C, Mingueneau M. Delbridge ARD, et al. Among authors: cullen p. Front Cell Neurosci. 2020 Dec 21;14:592005. doi: 10.3389/fncel.2020.592005. eCollection 2020. Front Cell Neurosci. 2020. PMID: 33473245 Free PMC article.
760 results