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Targeting splicing abnormalities in cancer.
Agrawal AA, Yu L, Smith PG, Buonamici S. Agrawal AA, et al. Among authors: smith pg. Curr Opin Genet Dev. 2018 Feb;48:67-74. doi: 10.1016/j.gde.2017.10.010. Epub 2017 Nov 12. Curr Opin Genet Dev. 2018. PMID: 29136527 Review.
H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers.
Seiler M, Yoshimi A, Darman R, Chan B, Keaney G, Thomas M, Agrawal AA, Caleb B, Csibi A, Sean E, Fekkes P, Karr C, Klimek V, Lai G, Lee L, Kumar P, Lee SC, Liu X, Mackenzie C, Meeske C, Mizui Y, Padron E, Park E, Pazolli E, Peng S, Prajapati S, Taylor J, Teng T, Wang J, Warmuth M, Yao H, Yu L, Zhu P, Abdel-Wahab O, Smith PG, Buonamici S. Seiler M, et al. Among authors: smith pg. Nat Med. 2018 May;24(4):497-504. doi: 10.1038/nm.4493. Epub 2018 Feb 19. Nat Med. 2018. PMID: 29457796 Free PMC article.
The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action.
Finci LI, Zhang X, Huang X, Zhou Q, Tsai J, Teng T, Agrawal A, Chan B, Irwin S, Karr C, Cook A, Zhu P, Reynolds D, Smith PG, Fekkes P, Buonamici S, Larsen NA. Finci LI, et al. Among authors: smith pg. Genes Dev. 2018 Feb 1;32(3-4):309-320. doi: 10.1101/gad.311043.117. Genes Dev. 2018. PMID: 29491137 Free PMC article.
Sensitivity to splicing modulation of BCL2 family genes defines cancer therapeutic strategies for splicing modulators.
Aird D, Teng T, Huang CL, Pazolli E, Banka D, Cheung-Ong K, Eifert C, Furman C, Wu ZJ, Seiler M, Buonamici S, Fekkes P, Karr C, Palacino J, Park E, Smith PG, Yu L, Mizui Y, Warmuth M, Chicas A, Corson L, Zhu P. Aird D, et al. Among authors: smith pg. Nat Commun. 2019 Jan 11;10(1):137. doi: 10.1038/s41467-018-08150-5. Nat Commun. 2019. PMID: 30635584 Free PMC article.
Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3' Splice Site Selection through Use of a Different Branch Point.
Darman RB, Seiler M, Agrawal AA, Lim KH, Peng S, Aird D, Bailey SL, Bhavsar EB, Chan B, Colla S, Corson L, Feala J, Fekkes P, Ichikawa K, Keaney GF, Lee L, Kumar P, Kunii K, MacKenzie C, Matijevic M, Mizui Y, Myint K, Park ES, Puyang X, Selvaraj A, Thomas MP, Tsai J, Wang JY, Warmuth M, Yang H, Zhu P, Garcia-Manero G, Furman RR, Yu L, Smith PG, Buonamici S. Darman RB, et al. Among authors: smith pg. Cell Rep. 2015 Nov 3;13(5):1033-45. doi: 10.1016/j.celrep.2015.09.053. Epub 2015 Oct 22. Cell Rep. 2015. PMID: 26565915 Free article.
Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins.
Lee SC, Dvinge H, Kim E, Cho H, Micol JB, Chung YR, Durham BH, Yoshimi A, Kim YJ, Thomas M, Lobry C, Chen CW, Pastore A, Taylor J, Wang X, Krivtsov A, Armstrong SA, Palacino J, Buonamici S, Smith PG, Bradley RK, Abdel-Wahab O. Lee SC, et al. Among authors: smith pg. Nat Med. 2016 Jun;22(6):672-8. doi: 10.1038/nm.4097. Epub 2016 May 2. Nat Med. 2016. PMID: 27135740 Free PMC article.
Physiologic Expression of Sf3b1(K700E) Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome Modulation.
Obeng EA, Chappell RJ, Seiler M, Chen MC, Campagna DR, Schmidt PJ, Schneider RK, Lord AM, Wang L, Gambe RG, McConkey ME, Ali AM, Raza A, Yu L, Buonamici S, Smith PG, Mullally A, Wu CJ, Fleming MD, Ebert BL. Obeng EA, et al. Among authors: smith pg. Cancer Cell. 2016 Sep 12;30(3):404-417. doi: 10.1016/j.ccell.2016.08.006. Cancer Cell. 2016. PMID: 27622333 Free PMC article.
Splicing modulators act at the branch point adenosine binding pocket defined by the PHF5A-SF3b complex.
Teng T, Tsai JH, Puyang X, Seiler M, Peng S, Prajapati S, Aird D, Buonamici S, Caleb B, Chan B, Corson L, Feala J, Fekkes P, Gerard B, Karr C, Korpal M, Liu X, T Lowe J, Mizui Y, Palacino J, Park E, Smith PG, Subramanian V, Wu ZJ, Zou J, Yu L, Chicas A, Warmuth M, Larsen N, Zhu P. Teng T, et al. Among authors: smith pg. Nat Commun. 2017 May 25;8:15522. doi: 10.1038/ncomms15522. Nat Commun. 2017. PMID: 28541300 Free PMC article.
738 results