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Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo.
Sebolt-Leopold JS, Dudley DT, Herrera R, Van Becelaere K, Wiland A, Gowan RC, Tecle H, Barrett SD, Bridges A, Przybranowski S, Leopold WR, Saltiel AR. Sebolt-Leopold JS, et al. Nat Med. 1999 Jul;5(7):810-6. doi: 10.1038/10533. Nat Med. 1999. PMID: 10395327
The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901.
Barrett SD, Bridges AJ, Dudley DT, Saltiel AR, Fergus JH, Flamme CM, Delaney AM, Kaufman M, LePage S, Leopold WR, Przybranowski SA, Sebolt-Leopold J, Van Becelaere K, Doherty AM, Kennedy RM, Marston D, Howard WA Jr, Smith Y, Warmus JS, Tecle H. Barrett SD, et al. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6501-4. doi: 10.1016/j.bmcl.2008.10.054. Epub 2008 Oct 15. Bioorg Med Chem Lett. 2008. PMID: 18952427
Dual inhibition of allosteric mitogen-activated protein kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) oncogenic targets with a bifunctional inhibitor.
Van Dort ME, Galbán S, Wang H, Sebolt-Leopold J, Whitehead C, Hong H, Rehemtulla A, Ross BD. Van Dort ME, et al. Bioorg Med Chem. 2015 Apr 1;23(7):1386-94. doi: 10.1016/j.bmc.2015.02.053. Epub 2015 Mar 6. Bioorg Med Chem. 2015. PMID: 25766633 Free PMC article.
Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon.
Haigis KM, Kendall KR, Wang Y, Cheung A, Haigis MC, Glickman JN, Niwa-Kawakita M, Sweet-Cordero A, Sebolt-Leopold J, Shannon KM, Settleman J, Giovannini M, Jacks T. Haigis KM, et al. Nat Genet. 2008 May;40(5):600-8. doi: 10.1038/ng.115. Epub 2008 Mar 30. Nat Genet. 2008. PMID: 18372904 Free PMC article.
Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras.
Lauchle JO, Kim D, Le DT, Akagi K, Crone M, Krisman K, Warner K, Bonifas JM, Li Q, Coakley KM, Diaz-Flores E, Gorman M, Przybranowski S, Tran M, Kogan SC, Roose JP, Copeland NG, Jenkins NA, Parada L, Wolff L, Sebolt-Leopold J, Shannon K. Lauchle JO, et al. Nature. 2009 Sep 17;461(7262):411-4. doi: 10.1038/nature08279. Epub 2009 Sep 2. Nature. 2009. PMID: 19727076 Free PMC article.
A role for K-ras in conferring resistance to the MEK inhibitor, CI-1040.
Wang Y, Van Becelaere K, Jiang P, Przybranowski S, Omer C, Sebolt-Leopold J. Wang Y, et al. Neoplasia. 2005 Apr;7(4):336-47. doi: 10.1593/neo.04532. Neoplasia. 2005. PMID: 15967111 Free PMC article.
Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition.
Ohren JF, Chen H, Pavlovsky A, Whitehead C, Zhang E, Kuffa P, Yan C, McConnell P, Spessard C, Banotai C, Mueller WT, Delaney A, Omer C, Sebolt-Leopold J, Dudley DT, Leung IK, Flamme C, Warmus J, Kaufman M, Barrett S, Tecle H, Hasemann CA. Ohren JF, et al. Nat Struct Mol Biol. 2004 Dec;11(12):1192-7. doi: 10.1038/nsmb859. Epub 2004 Nov 14. Nat Struct Mol Biol. 2004. PMID: 15543157
CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK).
Allen LF, Sebolt-Leopold J, Meyer MB. Allen LF, et al. Semin Oncol. 2003 Oct;30(5 Suppl 16):105-16. doi: 10.1053/j.seminoncol.2003.08.012. Semin Oncol. 2003. PMID: 14613031 Review.
Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies.
Lorusso PM, Adjei AA, Varterasian M, Gadgeel S, Reid J, Mitchell DY, Hanson L, DeLuca P, Bruzek L, Piens J, Asbury P, Van Becelaere K, Herrera R, Sebolt-Leopold J, Meyer MB. Lorusso PM, et al. J Clin Oncol. 2005 Aug 10;23(23):5281-93. doi: 10.1200/JCO.2005.14.415. Epub 2005 Jul 11. J Clin Oncol. 2005. PMID: 16009947 Clinical Trial.
BRAF mutation predicts sensitivity to MEK inhibition.
Solit DB, Garraway LA, Pratilas CA, Sawai A, Getz G, Basso A, Ye Q, Lobo JM, She Y, Osman I, Golub TR, Sebolt-Leopold J, Sellers WR, Rosen N. Solit DB, et al. Nature. 2006 Jan 19;439(7074):358-62. doi: 10.1038/nature04304. Epub 2005 Nov 6. Nature. 2006. PMID: 16273091 Free PMC article.
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