From haystack to needle: finding value with DNA encoded library technology at GSK

被引：72

作者：

Arico-Muendel, Christopher C. ^{[1
]}

机构：

[1] GlaxoSmithKline, 830 Winter St, Waltham, MA 02451 USA

来源：

MEDCHEMCOMM | 2016年 / 7卷 / 10期

关键词：

BCATM INHIBITORS; HIGHLY POTENT; BINDING MODE; IN-VITRO; DISCOVERY; ELT; OPTIMIZATION; ANTAGONISTS; ARYLAMINES; SELECTION;

D O I：

10.1039/c6md00341a

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA encoded library technology (ELT) provides access to broad chemical diversity through affinity selection. As an early adopter, GlaxoSmithKline enabled the development of ELT from proof of concept to full fledged contributor to the small molecule therapeutic pipeline. Unique benefits of the GSK incubation include uptake of large numbers of building blocks and privileged scaffolds, guidance on library design, and opportunities to add value beyond lead discovery. Soluble epoxide hydrolase and RIP1 kinase represent two case studies of ELT hits that have advanced into clinical studies. ELT also shows promise as a strategy to forecast target tractability. As an emerging technology, it benefits from incubation at the interface of industry and academia.

引用

页码：1898 / 1909

页数：12

共 32 条

[1]

[Anonymous], 2016, J MED CHEM, V59, DOI [10.1021/acs.jmedchem.5b01874, DOI 10.1021/ACS.JMEDCHEM.5B01874]

[2] Encoded Library Technology Screening of Hepatitis C Virus NS4B Yields a Small-Molecule Compound Series with In Vitro Replicon Activity [J].

Arico-Muendel, Christopher ;

Zhu, Zhengrong ;

Dickson, Hamilton ;

Parks, Derek ;

Keicher, Jesse ;

Deng, Jianghe ;

Aquilani, Leah ;

Coppo, Frank ;

Graybill, Todd ;

Lind, Kenneth ;

Peat, Andrew ;

Thomson, Michael .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2015, 59 (06) :3450-3459

[3] Design, synthesis and selection of DNA-encoded small-molecule libraries [J].

Clark, Matthew A. ;

Acharya, Raksha A. ;

Arico-Muendel, Christopher C. ;

Belyanskaya, Svetlana L. ;

Benjamin, Dennis R. ;

Carlson, Neil R. ;

Centrella, Paolo A. ;

Chiu, Cynthia H. ;

Creaser, Steffen P. ;

Cuozzo, John W. ;

Davie, Christopher P. ;

Ding, Yun ;

Franklin, G. Joseph ;

Franzen, Kurt D. ;

Gefter, Malcolm L. ;

Hale, Steven P. ;

Hansen, Nils J. V. ;

Israel, David I. ;

Jiang, Jinwei ;

Kavarana, Malcolm J. ;

Kelley, Michael S. ;

Kollmann, Christopher S. ;

Li, Fan ;

Lind, Kenneth ;

Mataruse, Sibongile ;

Medeiros, Patricia F. ;

Messer, Jeffrey A. ;

Myers, Paul ;

O'Keefe, Heather ;

Oliff, Matthew C. ;

Rise, Cecil E. ;

Satz, Alexander L. ;

Skinner, Steven R. ;

Svendsen, Jennifer L. ;

Tang, Lujia ;

van Vloten, Kurt ;

Wagner, Richard W. ;

Yao, Gang ;

Zhao, Baoguang ;

Morgan, Barry A. .

NATURE CHEMICAL BIOLOGY, 2009, 5 (09) :647-654

[4] Discovery and Optimization of Potent, Selective, and in Vivo Efficacious 2-Aryl Benzimidazole BCATm Inhibitors [J].

Deng, Hongfeng ;

Zhou, Jingye ;

Sundersingh, Flora ;

Messer, Jeffrey A. ;

Somers, Donald O. ;

Ajakane, Myriam ;

Arico-Muendel, Christopher C. ;

Beljean, Arthur ;

Belyanskaya, Svetlana L. ;

Bingham, Ryan ;

Blazensky, Emily ;

Boullay, Anne-Benedicte ;

Boursier, Eric ;

Chai, Jing ;

Carter, Paul ;

Chung, Chun-Wa ;

Daugan, Alain ;

Ding, Yun ;

Herry, Kenny ;

Hobbs, Clare ;

Humphries, Eric ;

Kollmann, Christopher ;

Van Loc Nguyen ;

Nicodeme, Edwige ;

Smith, Sarah E. ;

Dodic, Nerina ;

Ancellin, Nicolas .

ACS MEDICINAL CHEMISTRY LETTERS, 2016, 7 (04) :379-384

[5] Discovery, SAR, and X-ray Binding Mode Study of BCATm Inhibitors from a Novel DNA-Encoded Library [J].

Deng, Hongfeng ;

Zhou, Jingye ;

Sundersingh, Flora S. ;

Summerfield, Jennifer ;

Somers, Don ;

Messer, Jeffrey A. ;

Satz, Alexander L. ;

Ancellin, Nicolas ;

Arico-Muendel, Christopher C. ;

Bedard, Katie L. ;

Beljean, Arthur ;

Belyanskaya, Svetlana L. ;

Bingham, Ryan ;

Smith, Sarah E. ;

Boursier, Eric ;

Carter, Paul ;

Centrella, Paolo A. ;

Clark, Matthew A. ;

Chung, Chun-wa ;

Davie, Christopher P. ;

Delorey, Jennifer L. ;

Ding, Yun ;

Franklin, G. Joseph ;

Grady, LaShadric C. ;

Herry, Kenny ;

Hobbs, Clare ;

Kollmann, Christopher S. ;

Morgan, Barry A. ;

Kaushansky, Laura J. ;

Zhou, Quan .

ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (08) :919-924

[6] Discovery of Highly Potent and Selective Small Molecule ADAMTS-5 Inhibitors That Inhibit Human Cartilage Degradation via Encoded Library Technology (ELT) [J].

Deng, Hongfeng ;

O'Keefe, Heather ;

Davie, Christopher P. ;

Lind, Kenneth E. ;

Acharya, Raksha A. ;

Franklin, G. Joseph ;

Larkin, Jonathan ;

Matico, Rosalie ;

Neeb, Michael ;

Thompson, Monique M. ;

Lohr, Thomas ;

Gross, Jeffrey W. ;

Centrella, Paolo A. ;

O'Donovan, Gary K. ;

Bedard, Katie L. ;

van Vloten, Kurt ;

Mataruse, Sibongile ;

Skinner, Steven R. ;

Belyanskaya, Svetlana L. ;

Carpenter, Tiffany Y. ;

Shearer, Todd W. ;

Clark, Matthew A. ;

Cuozzo, John W. ;

Arico-Muendel, Christopher C. ;

Morgan, Barry A. .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (16) :7061-7079

[7] Discovery of Potent and Selective Inhibitors for ADAMTS-4 through DNA-Encoded Library Technology (ELT) [J].

Ding, Yun ;

O'Keefe, Heather ;

DeLorey, Jennifer L. ;

Israebt, David I. ;

Messer, Jeffrey A. ;

Chiu, Cynthia H. ;

Skinner, Steven R. ;

Matico, Rosalie E. ;

Murray-Thompson, Monique F. ;

Li, Fan ;

Clark, Matthew A. ;

Cuozzo, John W. ;

Arico-Muendel, Christopher ;

Morgan, Barry A. .

ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (08) :888-893

[8] Robust Suzuki-Miyaura Cross-Coupling on DNA-Linked Substrates [J].

Ding, Yun ;

Clark, Matthew A. .

ACS COMBINATORIAL SCIENCE, 2015, 17 (01) :1-4

[9] Discovery of Thieno[3,2-4-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3 [J].

Disch, Jeremy S. ;

Evindar, Ghotas ;

Chiu, Cynthia H. ;

Blum, Charles A. ;

Dai, Han ;

Jin, Lei ;

Schuman, Eli ;

Lind, Kenneth E. ;

Belyanskaya, Svetlana L. ;

Deng, Jianghe ;

Coppo, Frank ;

Aquilani, Leah ;

Graybill, Todd L. ;

Cuozzo, John W. ;

Lavu, Siva ;

Mao, Cheney ;

Vlasuk, George P. ;

Perni, Robert B. .

JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (09) :3666-3679

[10] Encoded Library Technology as a Source of Hits for the Discovery and Lead Optimization of a Potent and Selective Class of Bactericidal Direct Inhibitors of Mycobacterium tuberculosis InhA [J].

Encinas, Lourdes ;

O'Keefe, Heather ;

Neu, Margarete ;

Remuinan, Modesto J. ;

Patel, Amish M. ;

Guardia, Ana ;

Davie, Christopher P. ;

Perez-Macias, Natalia ;

Yang, Hongfang ;

Convery, Maire A. ;

Messer, Jeff A. ;

Perez-Herran, Esther ;

Centrella, Paolo A. ;

Alvarez-Gomez, Daniel ;

Clark, Matthew A. ;

Huss, Sophie ;

O'Donovan, Gary K. ;

Ortega-Muro, Fatima ;

McDowell, William ;

Castaneda, Pablo ;

Arico-Muendel, Christopher C. ;

Pajk, Stane ;

Rullas, Joaquin ;

Angulo-Barturen, Inigo ;

Alvarez-Ruiz, Emilio ;

Mendoza-Losana, Alfonso ;

Pages, Lluis Ballell ;

Castro-Pichel, Julia ;

Evindar, Ghotas .

JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (04) :1276-1288

← 1 2 3 4 →