Results 31 to 40 of about 692,160 (279)

Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors [PDF]

, 2023
Bivalent molecules consisting of groups connected through bridging linkers often exhibit strong target binding and unique biological effects. However, developing bivalent inhibitors with the desired activity is challenging due to the dual motif ...
Alexander, Rasch, Brian, Buckley, Calvin D. , Pham, Michael J., Eck, Tyler S. , Beyett, Earl W., May, Florian, Wittlinger, Brandon T, Oligny, Pamela A., Hershberger, Ilse K., Schaeffner, Erik M., Schaefer, Surbhi P., Chitnis, Blessing C. , Ogboo, Stefan A., Laufer, Tahereh, Damghani, David E. , Heppner, Daniel A., Urul, Tatiana, Shaurova, Antti, Poso, Ekaterina, Shevchenko   +19 more
core   +2 more sources

p185(BCR/ABL) has a lower sensitivity than p210(BCR/ABL) to the allosteric inhibitor GNF-2 in Philadelphia chromosome-positive acute lymphatic leukemia [PDF]

, 2011
Background: The t(9;22) translocation leads to the formation of the chimeric breakpoint cluster region/c-abl oncogene 1 (BCR/ABL) fusion gene on der22, the Philadelphia chromosome.
Mahajna, Jamal, Y. Najajreh, Ruthardt, Martin, M. Ruthardt, Ottmann, Oliver G., J. Mahajna, Mian, Afsar Ali, Mian, Afsar A., Metodieva, Anna, Najajreh, Yousef, A. Metodieva, A. A. Mian, O. G. Ottmann   +12 more
core   +1 more source

Allosteric inhibition of Aurora-A kinase by a synthetic vNAR domain [PDF]

Open Biology, 2016
The vast majority of clinically approved protein kinase inhibitors target the ATP-binding pocket directly. Consequently, many inhibitors have broad selectivity profiles and most have significant off-target effects.
Selena G. Burgess, Arkadiusz Oleksy, Tommaso Cavazza, Mark W. Richards, Isabelle Vernos, David Matthews, Richard Bayliss   +6 more
doaj   +1 more source

Imatinib disassembles the regulatory core of Abelson kinase by binding to its ATP site and not by binding to its myristoyl pocket [PDF]

Magnetic Resonance, 2022
It was recently reported (Xie et al., 2022) that the Abelson tyrosine kinase (Abl) ATP-site inhibitor imatinib also binds to Abl's myristoyl binding pocket, which is the target of allosteric Abl inhibitors.
S. Grzesiek, J. Paladini, J. Habazettl, R. Sonti   +3 more
doaj   +1 more source

Fumarate analogs act as allosteric inhibitors of the human mitochondrial NAD(P)+-dependent malic enzyme. [PDF]

PLoS ONE, 2014
Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon
Ju-Yi Hsieh, Jyung-Hurng Liu, Pai-Chun Yang, Chi-Li Lin, Guang-Yaw Liu, Hui-Chih Hung   +5 more
doaj   +1 more source

Fusion Strategy of DNA-Encoded Libraries Drives Discovery of Allosteric Inhibitors of SARS-CoV‑2 RdRp. [PDF]

JACS Au
Allosteric regulation is a central mechanism for modulating biological functions and offers an attractive strategy in drug discovery, particularly for targets considered challenging or \u201cundruggable.\u201d However, the discovery of allosteric ...
Li L, Wang X, Ding P, Shen X, Hu H, Wang X, Jin R, Wu X, Zhang Y, Lu W, Yue J, Xu HE, Yin W, Xu Y, Lu X.   +14 more
europepmc   +2 more sources

Resistance to Allosteric Inhibitors

Journal of Molecular Biology
Allosteric inhibitors have emerged as powerful therapeutic agents capable of overcoming resistance mutations that impair the efficacy of orthosteric inhibitors. However, resistance to allosteric inhibitors can also arise, posing a challenge to their long-term effectiveness.
Outhwaite, Ian R., Kwan, Isabelle, Leyte-Vidal, Ariel, Shah, Neil P., Bahar, Ivet, Seeliger, Markus A.   +5 more
openaire   +4 more sources

Binding Modes of Xanthine‐Derived Selective Allosteric Site Inhibitors of MTHFD2

ChemistryOpen, 2023
Methylenetetrahydrofolate dehydrogenase (MTHFD2) is a mitochondrial enzyme involved in 1 C metabolism that is upregulated in various cancer cells, but absent in normal proliferating cells. Xanthine derivatives are the first selective inhibitors of MTHFD2
Dr. Vibhu Jha, Prof. Dr. Leif A. Eriksson   +1 more
doaj   +1 more source

Biochemical pharmacology of the positive allosteric modulation of the GABAb receptor "in Vitro" and "in Vivo" [PDF]

, 2007
Allosteric modulators of G-protein coupled receptors (GPCRs) interact with binding sites on the receptor molecule that are topographically distinct from the classic orthosteric site.
Gjoni, Tina
core   +1 more source

Insights into the binding mode of MEK type-III inhibitors. A step towards discovering and designing allosteric kinase inhibitors across the human kinome. [PDF]

PLoS ONE, 2017
Protein kinases are critical drug targets for treating a large variety of human diseases. Type-III kinase inhibitors have attracted increasing attention as highly selective therapeutics.
Zheng Zhao, Lei Xie, Philip E Bourne
doaj   +1 more source