519
Views
46
CrossRef citations to date
0
Altmetric
Reviews

Novel γ-secretase modulators for the treatment of Alzheimer's disease: a review focusing on patents from 2010 to 2012

, , &
Pages 1349-1366 | Published online: 23 Jul 2013

Keep up to date with the latest research on this topic with citation updates for this article.

Read on this site (2)

Rongrong Li, Xuefeng Wang, Yuqin Liu, Shuo Zhang & Omer Hanif. (2021) Research status and collaboration analysis based on big data mining: an empirical study of Alzheimer's disease. Technology Analysis & Strategic Management 33:4, pages 379-395.
Read now
Julius Pollinger & Daniel Merk. (2017) Therapeutic applications of the versatile fatty acid mimetic WY14643. Expert Opinion on Therapeutic Patents 27:4, pages 517-525.
Read now

Articles from other publishers (44)

Jiachen Wen, Dan Liu & Linxiang Zhao. (2022) Small molecules targeting γ-secretase and their potential biological applications. European Journal of Medicinal Chemistry 232, pages 114169.
Crossref
Kevin D. Rynearson, Ronald N. Buckle, R. Jason Herr, Nicholas J. Mayhew, Xinchao Chen, William D. Paquette, Samuel A. Sakwa, Jinhai Yang, Keith D. Barnes, Phuong Nguyen, William C. Mobley, Graham Johnson, Juinn H. Lin, Rudolph E. Tanzi & Steven L. Wagner. (2020) Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators. Bioorganic & Medicinal Chemistry 28:22, pages 115734.
Crossref
Pengju Nie, Abhishek Vartak & Yue-Ming Li. (2020) γ-Secretase inhibitors and modulators: Mechanistic insights into the function and regulation of γ-Secretase. Seminars in Cell & Developmental Biology 105, pages 43-53.
Crossref
Rosa María Rodríguez Sarmiento, Caterina Bissantz, Johan Bylund, Anja Limberg, Werner Neidhart, Roland Jakob-Roetne, Lisha Wang & Karlheinz Baumann. (2020) Stepwise Design of γ-Secretase Modulators with an Advanced Profile by Judicious Coordinated Structural Replacements and an Unconventional Phenyl Ring Bioisostere. Journal of Medicinal Chemistry 63:15, pages 8534-8553.
Crossref
François P. Bischoff, Adriana Ingrid Velter, Garrett Minne, Serge Pieters, Didier Berthelot, Michel De Cleyn, Harrie J.M. Gijsen, Gregor Macdonald, Michel Surkyn, Sven Van Brandt, Yves Van Roosbroeck, Chiara Zavattaro, Marc Mercken, Nigel Austin, Deborah Dhuyvetter, Herman Borghys, Ishtiyaque Ahmad & Swapan Kumar Samanta. (2019) Design and synthesis of a novel series of cyanoindole derivatives as potent γ-secretase modulators. Bioorganic & Medicinal Chemistry Letters 29:14, pages 1737-1745.
Crossref
Longfei Xie, Christopher W. am Ende, Martin Pettersson, Danica A. Rankic, Neal W. Sach, Subbas Sakya & John M. Humphrey. (2019) Synthesis of Pyridopyrazine-1,6-dione γ-Secretase Modulators via Selective 4-Methylimidazole N 1 -Buchwald Arylation . The Journal of Organic Chemistry 84:8, pages 4921-4925.
Crossref
Miguel Maia & Emília Sousa. (2019) BACE-1 and γ-Secretase as Therapeutic Targets for Alzheimer’s Disease. Pharmaceuticals 12:1, pages 41.
Crossref
Kenneth M. Boy, Jason M. Guernon, Dmitry S. Zuev, Li Xu, Yunhui Zhang, Jianliang Shi, Lawrence R. Marcin, Mendi A. Higgins, Yong-Jin Wu, Subramaniam Krishnananthan, Jianqing Li, Ashok Trehan, Daniel Smith, Jeremy H. Toyn, Jere E. Meredith, Catherine R. Burton, S. Roy Kimura, Tatyana Zvyaga, Xiaoliang Zhuo, Kimberley A. Lentz, James E. Grace, Rex Denton, John S. Morrison, Arvind Mathur, Charles F. Albright, Michael K. Ahlijanian, Richard E. Olson, Lorin A. Thompson & John E. Macor. (2019) Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481. ACS Medicinal Chemistry Letters 10:3, pages 312-317.
Crossref
Kai Gerlach, Scott Hobson, Christian Eickmeier, Ulrike Groß, Clemens Braun, Peter Sieger, Michel Garneau, Stefan Hoerer & Niklas Heine. (2018) Discovery of tetrahydroindazoles as a novel class of potent and in vivo efficacious gamma secretase modulators. Bioorganic & Medicinal Chemistry 26:12, pages 3227-3241.
Crossref
Douglas S. Johnson, Yue-Ming Li, Martin Pettersson & Peter H. St George-Hyslop. (2017) Structural and Chemical Biology of Presenilin Complexes. Cold Spring Harbor Perspectives in Medicine 7:12, pages a024067.
Crossref
Paola Gordillo Guerra, Paolo Clerici & Laurent Micouin. (2017) Modular Access to N-Substituted cis 5-Amino-3-hydroxypiperidines . The Journal of Organic Chemistry 82:14, pages 7689-7694.
Crossref
Steven H. L. Verhelst. (2017) Intramembrane proteases as drug targets. The FEBS Journal 284:10, pages 1489-1502.
Crossref
Martin Pettersson, Douglas S. Johnson, Danica A. Rankic, Gregory W. Kauffman, Christopher W. am Ende, Todd W. Butler, Brian Boscoe, Edelweiss Evrard, Christopher J. Helal, John M. Humphrey, Antonia F. Stepan, Cory M. Stiff, Eddie Yang, Longfei Xie, Kelly R. Bales, Eva Hajos-Korcsok, Stephen Jenkinson, Betty Pettersen, Leslie R. Pustilnik, David S. Ramirez, Stefanus J. Steyn, Kathleen M. Wood & Patrick R. Verhoest. (2017) Discovery of cyclopropyl chromane-derived pyridopyrazine-1,6-dione γ-secretase modulators with robust central efficacy. MedChemComm 8:4, pages 730-743.
Crossref
Matthew G. Bursavich, Bryce A. Harrison, Raksha Acharya, Donald E. Costa, Emily A. Freeman, Hilliary E. Hodgdon, Lori A. Hrdlicka, Hong Jin, Sudarshan Kapadnis, Jeffrey S. Moffit, Deirdre A. Murphy, Scott Nolan, Holger Patzke, Cuyue Tang, Melody Wen, Gerhard Koenig, Jean-François Blain & Duane A. Burnett. (2017) Design, Synthesis, and Evaluation of a Novel Series of Oxadiazine Gamma Secretase Modulators for Familial Alzheimer’s Disease. Journal of Medicinal Chemistry 60:6, pages 2383-2400.
Crossref
A. Hall & A.I. Velter. 2017. Comprehensive Medicinal Chemistry III. Comprehensive Medicinal Chemistry III 280 325 .
Douglas S. Johnson & Martin Pettersson. 2017. Alzheimer’s Disease II. Alzheimer’s Disease II 87 118 .
Bernd Schröder & Paul Saftig. (2016) Intramembrane proteolysis within lysosomes. Ageing Research Reviews 32, pages 51-64.
Crossref
Xiao-dan Guo, Guang-long Sun, Ting-ting Zhou, Xin Xu, Zhi-yuan Zhu, Vatcharin Rukachaisirikul, Li-hong Hu & Xu Shen. (2016) Small molecule LX2343 ameliorates cognitive deficits in AD model mice by targeting both amyloid β production and clearance. Acta Pharmacologica Sinica 37:10, pages 1281-1297.
Crossref
Matthew G. Bursavich, Bryce A. Harrison & Jean-François Blain. (2016) Gamma Secretase Modulators: New Alzheimer’s Drugs on the Horizon?. Journal of Medicinal Chemistry 59:16, pages 7389-7409.
Crossref
Takafumi Takai, Tatsuki Koike, Minoru Nakamura, Yuichi Kajita, Toshiro Yamashita, Naohiro Taya, Tetsuya Tsukamoto, Tomomichi Watanabe, Koji Murakami, Tomoko Igari & Makoto Kamata. (2016) Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives as γ-secretase modulators (Part 2). Bioorganic & Medicinal Chemistry 24:14, pages 3192-3206.
Crossref
H. D. Soares, M. Gasior, J. H. Toyn, J.-S. Wang, Q. Hong, F. Berisha, M. T. Furlong, J. Raybon, K. A. Lentz, F. Sweeney, N. Zheng, B. Akinsanya, R. M. Berman, L. A. Thompson, R. E. Olson, J. Morrison, D. M. Drexler, J. E. Macor, C. F. Albright, M. K. Ahlijanian & M. AbuTarif. (2016) The  -Secretase Modulator, BMS-932481, Modulates A  Peptides in the Plasma and Cerebrospinal Fluid of Healthy Volunteers. Journal of Pharmacology and Experimental Therapeutics 358:1, pages 138-150.
Crossref
Martin Pettersson, Xinjun Hou, Max Kuhn, Travis T. Wager, Gregory W. Kauffman & Patrick R. Verhoest. (2016) Quantitative Assessment of the Impact of Fluorine Substitution on P-Glycoprotein (P-gp) Mediated Efflux, Permeability, Lipophilicity, and Metabolic Stability. Journal of Medicinal Chemistry 59:11, pages 5284-5296.
Crossref
Yong-Jin Wu, Yunhui Zhang, Jeremy H. Toyn, John E. Macor & Lorin A. Thompson. (2016) Synthesis of pyrimido[4,5- c ]azepine- and pyrimido[4,5- c ]oxepine-based γ-secretase modulators. Bioorganic & Medicinal Chemistry Letters 26:6, pages 1554-1557.
Crossref
O. G. Tatarnikova, M. A. Orlov & N. V. Bobkova. (2016) Beta-Amyloid and Tau-Protein: Structure, Interaction, and Prion-Like Properties. Biochemistry (Moscow) 80:13, pages 1800-1819.
Crossref
Laia Montoliu-Gaya & Sandra Villegas. (2015) Protein structures in Alzheimer's disease: The basis for rationale therapeutic design. Archives of Biochemistry and Biophysics 588, pages 1-14.
Crossref
Takafumi Takai, Yasutaka Hoashi, Yoshihide Tomata, Sachie Morimoto, Minoru Nakamura, Tomomichi Watanabe, Tomoko Igari & Tatsuki Koike. (2015) Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives as γ-secretase modulators. Bioorganic & Medicinal Chemistry Letters 25:19, pages 4245-4249.
Crossref
Christian Fischer, Susan L. Zultanski, Hua Zhou, Joey L. Methot, Sanjiv Shah, Ikuo Hayashi, Bethany L. Hughes, Christopher M. Moxham, Nathan W. Bays, Nadya Smotrov, Armetta D. Hill, Bo-Sheng Pan, Zhenhua Wu, Lily Y. Moy, Flobert Tanga, Candia Kenific, Jonathan C. Cruz, Deborah Walker, Melanie Bouthillette, George N. Nikov, Sujal V. Deshmukh, Valentina V. Jeliazkova-Mecheva, Damaris Diaz, Maria S. Michener, Jacquelynn J. Cook, Benito Munoz & Mark S. Shearman. (2015) Discovery of novel triazolobenzazepinones as γ-secretase modulators with central Aβ42 lowering in rodents and rhesus monkeys. Bioorganic & Medicinal Chemistry Letters 25:17, pages 3488-3494.
Crossref
Joey L. Methot, Christian Fischer, Chaomin Li, Alexey Rivkin, Sean P. Ahearn, William Colby Brown, Sam Kattar, Elizabeth Kelley, Dawn M. Mampreian, Adam Schell, Andrew Rosenau, Hua Zhou, Richard Ball, Sujal V. Deshmukh, Valentina V. Jeliazkova-Mecheva, Damaris Diaz, Lily Y. Moy, Candia M. Kenific, Chris Moxham, Sanjiv Shah, Hugh Nuthall, Alexander A. Szewczak, Armetta Hill, Bethany Hughes, Nadya Smotrov, Benito Munoz, Thomas A. Miller & Mark S. Shearman. (2015) Potent benzoazepinone γ-secretase modulators with improved bioavailability. Bioorganic & Medicinal Chemistry Letters 25:17, pages 3495-3500.
Crossref
Daniel Merk, Martina Zettl, Dieter Steinhilber, Oliver Werz & Manfred Schubert-Zsilavecz. (2015) Pirinixic acids: flexible fatty acid mimetics with various biological activities. Future Medicinal Chemistry 7:12, pages 1597-1616.
Crossref
Anna Bogstedt, Maria Groves, Keith Tan, Rajesh Narwal, Mary McFarlane & Kina Höglund. (2015) Development of Immunoassays for the Quantitative Assessment of Amyloid-β in the Presence of Therapeutic Antibody: Application to Pre-Clinical Studies. Journal of Alzheimer's Disease 46:4, pages 1091-1101.
Crossref
Martin Pettersson, Douglas S. Johnson, John M. Humphrey, Todd W. Butler, Christopher W. am Ende, Benjamin A. Fish, Michael E. Green, Gregory W. Kauffman, Patrick B. Mullins, Christopher J. O’Donnell, Antonia F. Stepan, Cory M. Stiff, Chakrapani Subramanyam, Tuan P. Tran, Beth Cooper Vetelino, Eddie Yang, Longfei Xie, Kelly R. Bales, Leslie R. Pustilnik, Stefanus J. Steyn, Kathleen M. Wood & Patrick R. Verhoest. (2015) Design of Pyridopyrazine-1,6-dione γ-Secretase Modulators that Align Potency, MDR Efflux Ratio, and Metabolic Stability. ACS Medicinal Chemistry Letters 6:5, pages 596-601.
Crossref
C. Bohm, F. Chen, J. Sevalle, S. Qamar, R. Dodd, Y. Li, G. Schmitt-Ulms, P.E. Fraser & P.H. St George-Hyslop. (2015) Current and future implications of basic and translational research on amyloid-β peptide production and removal pathways. Molecular and Cellular Neuroscience 66, pages 3-11.
Crossref
Takafumi Takai, Tatsuki Koike, Eiji Honda, Yuichi Kajita, Minoru Nakamura, Sachie Morimoto, Yasutaka Hoashi, Makoto Kamata, Tomomichi Watanabe, Tomoko Igari & Jun Terauchi. (2015) Design and synthesis of piperazine derivatives as a novel class of γ-secretase modulators that selectively lower Aβ42 production. Bioorganic & Medicinal Chemistry 23:9, pages 1923-1934.
Crossref
Jed L. Hubbs, Nathan O. Fuller, Wesley F. Austin, Ruichao Shen, Jianguo Ma, Zhen Gong, Jian Li, Timothy D. McKee, Robyn M.B. Loureiro, Barbara Tate, Jo Ann Dumin, Jeffrey Ives & Brian S. Bronk. (2015) Minimization of drug–drug interaction risk and candidate selection in a natural product-based class of gamma-secretase modulators. Bioorganic & Medicinal Chemistry Letters 25:7, pages 1621-1626.
Crossref
Martin Pettersson, Douglas S. Johnson, John M. Humphrey, Christopher W. am Ende, Edelweiss Evrard, Ivan Efremov, Gregory W. Kauffman, Antonia F. Stepan, Cory M. Stiff, Longfei Xie, Kelly R. Bales, Eva Hajos-Korcsok, Heather E. Murrey, Leslie R. Pustilnik, Stefanus J. Steyn, Kathleen M. Wood & Patrick R. Verhoest. (2015) Discovery of indole-derived pyridopyrazine-1,6-dione γ-secretase modulators that target presenilin. Bioorganic & Medicinal Chemistry Letters 25:4, pages 908-913.
Crossref
Xian Zhang, Yanfang Li, Huaxi Xu & Yun-wu Zhang. (2014) The γ-secretase complex: from structure to function. Frontiers in Cellular Neuroscience 8.
Crossref
Yi Li, Christopher Bohm, Roger Dodd, Fusheng Chen, Seema Qamar, Gerold Schmitt-Ulms, Paul E Fraser & Peter H St George-Hyslop. (2014) Structural biology of presenilin 1 complexes. Molecular Neurodegeneration 9:1.
Crossref
Adriana I. Velter, François P. Bischoff, Didier Berthelot, Michel De Cleyn, Daniel Oehlrich, Libuse Jaroskova, Gregor Macdonald, Garrett Minne, Serge Pieters, Frederik Rombouts, Sven Van Brandt, Yves Van Roosbroeck, Michel Surkyn, Andrés A. Trabanco, Gary Tresadern, Tongfei Wu, Herman Borghys, Marc Mercken, Chantal Masungi & Harrie Gijsen. (2014) Anilinotriazoles as potent gamma secretase modulators. Bioorganic & Medicinal Chemistry Letters 24:24, pages 5805-5813.
Crossref
Eliza Barnwell, Vasudevaraju Padmaraju, Robert Baranello, Javier Pacheco-Quinto, Craig Crosson, Zsolt Ablonczy, Elizabeth Eckman, Christopher B. Eckman, Viswanathan Ramakrishnan, Nigel H. Greig, Miguel A. Pappolla & Kumar Sambamurti. (2014) Evidence of a Novel Mechanism for Partial γ-Secretase Inhibition Induced Paradoxical Increase in Secreted Amyloid β Protein. PLoS ONE 9:3, pages e91531.
Crossref
Martin Pettersson, Douglas S. Johnson, Chakrapani Subramanyam, Kelly R. Bales, Christopher W. am Ende, Benjamin A. Fish, Michael E. Green, Gregory W. Kauffman, Patrick B. Mullins, Thayalan Navaratnam, Subas M. Sakya, Cory M. Stiff, Tuan P. Tran, Longfei Xie, Liming Zhang, Leslie R. Pustilnik, Beth C. Vetelino, Kathleen M. Wood, Nikolay Pozdnyakov, Patrick R. Verhoest & Christopher J. O’Donnell. (2014) Design, Synthesis, and Pharmacological Evaluation of a Novel Series of Pyridopyrazine-1,6-dione γ-Secretase Modulators. Journal of Medicinal Chemistry 57:3, pages 1046-1062.
Crossref
Gaetano Malgieri & Giuseppe Grasso. (2014) The clearance of misfolded proteins in neurodegenerative diseases by zinc metalloproteases: An inorganic perspective. Coordination Chemistry Reviews 260, pages 139-155.
Crossref
Jeremy H Toyn & Michael K Ahlijanian. (2014) Interpreting Alzheimer’s disease clinical trials in light of the effects on amyloid-β. Alzheimer's Research & Therapy 6:2, pages 14.
Crossref
Adrian Hall & Toshal R. Patel. 2014. 101 145 .
Ramón Cacabelos, Pablo Cacabelos, Clara Torrellas, Iván Tellado & Juan C. Carril. 2014. Pharmacogenomics in Drug Discovery and Development. Pharmacogenomics in Drug Discovery and Development 323 556 .

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.