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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.
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.
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
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.
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
A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors.
Saura C, Roda D, Roselló S, Oliveira M, Macarulla T, Pérez-Fidalgo JA, Morales-Barrera R, Sanchis-García JM, Musib L, Budha N, Zhu J, Nannini M, Chan WY, Sanabria Bohórquez SM, Meng RD, Lin K, Yan Y, Patel P, Baselga J, Tabernero J, Cervantes A. Saura C, et al. Among authors: lin k. Cancer Discov. 2017 Jan;7(1):102-113. doi: 10.1158/2159-8290.CD-16-0512. Epub 2016 Nov 21. Cancer Discov. 2017. PMID: 27872130 Free PMC article. Clinical Trial.
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
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