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Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors.
Blake JF, Xu R, Bencsik JR, Xiao D, Kallan NC, Schlachter S, Mitchell IS, Spencer KL, Banka AL, Wallace EM, Gloor SL, Martinson M, Woessner RD, Vigers GP, Brandhuber BJ, Liang J, Safina BS, Li J, Zhang B, Chabot C, Do S, Lee L, Oeh J, Sampath D, Lee BB, Lin K, Liederer BM, Skelton NJ. Blake JF, et al. Among authors: lin k. J Med Chem. 2012 Sep 27;55(18):8110-27. doi: 10.1021/jm301024w. Epub 2012 Sep 18. J Med Chem. 2012. PMID: 22934575
Distinct resistance mechanisms arise to allosteric vs. ATP-competitive AKT inhibitors.
Savill KMZ, Lee BB, Oeh J, Lin J, Lin E, Chung WJ, Young A, Chen W, Miś M, Mesh K, Eastham J, Gnad F, Jiang Z, Stawiski EW, Haley B, Daemen A, Wang X, Koeppen H, Modrusan Z, Martin SE, Sampath D, Lin K. Savill KMZ, et al. Among authors: lin e, lin j, lin k. Nat Commun. 2022 Apr 19;13(1):2057. doi: 10.1038/s41467-022-29655-0. Nat Commun. 2022. PMID: 35440108 Free PMC article.
Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models.
Lin J, Sampath D, Nannini MA, Lee BB, Degtyarev M, Oeh J, Savage H, Guan Z, Hong R, Kassees R, Lee LB, Risom T, Gross S, Liederer BM, Koeppen H, Skelton NJ, Wallin JJ, Belvin M, Punnoose E, Friedman LS, Lin K. Lin J, et al. Among authors: lin k. Clin Cancer Res. 2013 Apr 1;19(7):1760-72. doi: 10.1158/1078-0432.CCR-12-3072. Epub 2013 Jan 3. Clin Cancer Res. 2013. PMID: 23287563
Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents.
Degtyarev M, De Mazière A, Orr C, Lin J, Lee BB, Tien JY, Prior WW, van Dijk S, Wu H, Gray DC, Davis DP, Stern HM, Murray LJ, Hoeflich KP, Klumperman J, Friedman LS, Lin K. Degtyarev M, et al. Among authors: lin j, lin k. J Cell Biol. 2008 Oct 6;183(1):101-16. doi: 10.1083/jcb.200801099. J Cell Biol. 2008. PMID: 18838554 Free PMC article.
Disruption of PH-kinase domain interactions leads to oncogenic activation of AKT in human cancers.
Parikh C, Janakiraman V, Wu WI, Foo CK, Kljavin NM, Chaudhuri S, Stawiski E, Lee B, Lin J, Li H, Lorenzo MN, Yuan W, Guillory J, Jackson M, Rondon J, Franke Y, Bowman KK, Sagolla M, Stinson J, Wu TD, Wu J, Stokoe D, Stern HM, Brandhuber BJ, Lin K, Skelton NJ, Seshagiri S. Parikh C, et al. Among authors: lin j, lin k. Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19368-73. doi: 10.1073/pnas.1204384109. Epub 2012 Nov 7. Proc Natl Acad Sci U S A. 2012. PMID: 23134728 Free PMC article.
Autophagy, an Achilles' heel AKTing against cancer?
Degtyarev M, De Mazière A, Klumperman J, Lin K. Degtyarev M, et al. Among authors: lin k. Autophagy. 2009 Apr;5(3):415-8. doi: 10.4161/auto.5.3.7827. Autophagy. 2009. PMID: 19305139
The Akt DUBbed InAktive.
Lin K. Lin K. Sci Signal. 2013 Jan 8;6(257):pe1. doi: 10.1126/scisignal.2003864. Sci Signal. 2013. PMID: 23300338
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