Results 51 to 60 of about 692,160 (279)

5,6,7,8-Tetrahydro-1,6-naphthyridine Derivatives as Potent HIV-1-Integrase-Allosteric-Site Inhibitors

, 2019
A series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives targeting the allosteric lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractive target for antiviral chemotherapy, was prepared and screened for ...
Timothy Connolly (1754563), Dawn D. Parker (1834201), Christopher Cianci (6240926), Susan Jenkins (1834318), Kevin M. Peese (1457527), Barry L. Johnson (6240911), Robert T. Nolte (471200), Chen Li (54018), Hal A. Lewis (1399384), Christopher W. Allard (6240908), Brian McAuliffe (6240920), Nicholas A. Meanwell (362044), Manoj Patel (6240914), Mark Krystal (364355), Ping Zhang (86495), Michael A. Walker (1754566), Beatrice Minassian (6240923), Kevin Kish (1399378), Jean Simmermacher (5101232), Margaret E. Sorensen (6240917), B. Narasimhulu Naidu (2686801)   +20 more
core   +2 more sources

The mechanism of allosteric inhibition of protein tyrosine phosphatase 1B.

PLoS ONE, 2014
As the prototypical member of the PTP family, protein tyrosine phosphatase 1B (PTP1B) is an attractive target for therapeutic interventions in type 2 diabetes.
Shuai Li, Jingmiao Zhang, Shaoyong Lu, Wenkang Huang, Lv Geng, Qiancheng Shen, Jian Zhang   +6 more
doaj   +1 more source

Can We Exploit β-Lactamases Intrinsic Dynamics for Designing More Effective Inhibitors?

Antibiotics, 2020
β-lactamases (BLs) represent the most frequent cause of antimicrobial resistance in Gram-negative bacteria. Despite the continuous efforts in the development of BL inhibitors (BLIs), new BLs able to hydrolyze the last developed antibiotics rapidly emerge.
Eleonora Gianquinto, Donatella Tondi, Giulia D'Arrigo, Loretta Lazzarato, Francesca Spyrakis   +4 more
doaj   +1 more source

An Allosteric Inhibitor of Protein Arginine Methyltransferase 3 [PDF]

Structure, 2012
PRMT3, a protein arginine methyltransferase, has been shown to influence ribosomal biosynthesis by catalyzing the dimethylation of the 40S ribosomal protein S2. Although PRMT3 has been reported to be a cytosolic protein, it has been shown to methylate histone H4 peptide (H4 1-24) in vitro.
Siarheyeva, Alena, Senisterra, Guillermo, Allali-Hassani, Abdellah, Dong, Aiping, Dobrovetsky, Elena, Wasney, Gregory A., Chau, Irene, Marcellus, Richard, Hajian, Taraneh, Liu, Feng, Korboukh, Ilia, Smil, David, Bolshan, Yuri, Min, Jinrong, Wu, Hong, Zeng, Hong, Loppnau, Peter, Poda, Gennadiy, Griffin, Carly, Aman, Ahmed, Brown, Peter J., Jin, Jian, Al-awar, Rima, Arrowsmith, Cheryl H., Schapira, Matthieu, Vedadi, Masoud   +25 more
openaire   +2 more sources

Discovery of 2,6-Dimethylpiperazines as Allosteric Inhibitors of CPS1

ACS Medicinal Chemistry Letters, 2020
Carbamoyl phosphate synthetase 1 (CPS1) is a potential synthetic lethal target in LKB1-deficient nonsmall cell lung cancer, where its overexpression supports the production of pyrimidine synthesis. In other cancer types, CPS1 overexpression and activity may prevent the accumulation of toxic levels of intratumoral ammonia to support tumor growth. Herein
Alan Rolfe, Shihua Yao, Toung-Vi Nguyen, Kiyoyuki Omoto, Federico Colombo, Milena Virrankoski, Frédéric H. Vaillancourt, Lihua Yu, Andrew Cook, Dominic Reynolds, Stephanos Ioannidis, Ping Zhu, Nicholas A. Larsen, David M. Bolduc   +13 more
openaire   +3 more sources

ATP Is an Allosteric Inhibitor of Coxsackievirus B3 Polymerase [PDF]

Biochemistry, 2016
The RNA-dependent RNA polymerases from positive-strand RNA viruses, such as picornaviruses and flaviviruses, close their active sites for catalysis via a unique NTP-induced conformational change in the palm domain. Combined with a fully prepositioned templating nucleotide, this mechanism is error-prone and results in a distribution of random mutations ...
Jonathan P, Karr, Olve B, Peersen
openaire   +2 more sources

Engineering peptides into antibodies—opportunities and strategies for therapeutic innovation

FEBS Letters, EarlyView.
Peptides and antibodies occupy complementary therapeutic niches. Peptides recognize difficult targets in a compact format, while antibodies add specificity, long half‐life, and effector functions. This review examines strategies that merge both modalities—peptide grafting into loops, terminal and Fc fusions, and bioconjugation—highlighting how ...
Jinling Wang, Ruslana Romaniuk, Hristo L. Svilenov   +2 more
wiley   +1 more source

Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors [PDF]

Journal of Medicinal Chemistry, 2019
SHP2 is a nonreceptor protein tyrosine phosphatase within the mitogen-activated protein kinase (MAPK) pathway controlling cell growth, differentiation, and oncogenic transformation. SHP2 also participates in the programed cell death pathway (PD-1/PD-L1) governing immune surveillance.
Jeffrey T. Bagdanoff, Zhouliang Chen, Michael Acker, Ying-Nan Chen, Homan Chan, Michael Dore, Brant Firestone, Michelle Fodor, Jorge Fortanet, Murphy Hentemann, Mitsunori Kato, Robert Koenig, Laura R. LaBonte, Shumei Liu, Movarid Mohseni, Rukundo Ntaganda, Patrick Sarver, Troy Smith, Martin Sendzik, Travis Stams, Stan Spence, Christopher Towler, Hongyun Wang, Ping Wang, Sarah L. Williams, Matthew J. LaMarche   +25 more
openaire   +2 more sources

The Shewanella oneidensis Fic enzyme SoFic targets the switch‐I region of EF‐Tu for AMPylation

FEBS Letters, EarlyView.
Fic enzymes mediate diverse post‐translational modifications across all domains of life, including AMPylation. Prokaryotic EF‐Tu can be AMPylated and deAMPylated by the conserved Fic enzyme SoFic. Structural and biochemical approaches were used to characterize the effect of AMPylation on EF‐Tu, SoFic's enzymatic activities, and the enzyme‐target ...
Svenja Runge, Vivian Pogenberg, Alexander Baumgart, Bente Siebels, Hartmut Schlüter, Michael Hecht‐Bucher, Aymelt Itzen   +6 more
wiley   +1 more source

Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors

eLife
The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction of BRAF dimers, but why activation rather than inhibition occurs remains unclear.
Damien M Rasmussen, Manny M Semonis, Joseph T Greene, Joseph M Muretta, Andrew R Thompson, Silvia Toledo Ramos, David D Thomas, William CK Pomerantz, Tanya S Freedman, Nicholas M Levinson   +9 more
doaj   +1 more source