scholarly journals The Structural Basis ofCryptosporidium-Specific IMP Dehydrogenase Inhibitor Selectivity

2010 ◽  
Vol 132 (18) ◽  
pp. 6610-6610
Author(s):  
Iain S. MacPherson ◽  
Sivapriya Kirubakaran ◽  
Suresh Kumar Gorla ◽  
Thomas V. Riera ◽  
J. Alejandro D’Aquino ◽  
...  
Keyword(s):  
Structural Basis ◽  
Imp Dehydrogenase ◽  
Inhibitor Selectivity

scholarly journals The Structural Basis of Cryptosporidium-Specific IMP Dehydrogenase Inhibitor Selectivity

2010 ◽  
Vol 132 (4) ◽  
pp. 1230-1231 ◽  
Author(s):  
Iain S. MacPherson ◽  
Sivapriya Kirubakaran ◽  
Suresh Kumar Gorla ◽  
Thomas V. Riera ◽  
J. Alejandro D’Aquino ◽  
...  
Keyword(s):  
Structural Basis ◽  
Imp Dehydrogenase ◽  
Inhibitor Selectivity

CLINICAL AND TOXICOLOGICAL RELEVANCE OF CYP2C9: Drug-Drug Interactions and Pharmacogenetics

2005 ◽  
Vol 45 (1) ◽  
pp. 477-494 ◽  
Author(s):  
Allan E. Rettie ◽  
Jeffrey P. Jones
Keyword(s):  
Oral Anticoagulants ◽  
Quantitative Structure Activity Relationship ◽  
Structural Basis ◽  
Cytochrome P450 Enzyme ◽  
Metabolic Clearance ◽  
Structure Activity ◽  
Oral Hypoglycemics ◽  
P450 Enzyme ◽  
Qsar Models ◽  
Inhibitor Selectivity

CYP2C9 is a major cytochrome P450 enzyme that is involved in the metabolic clearance of a wide variety of therapeutic agents, including nonsteroidal antiinflammatories, oral anticoagulants, and oral hypoglycemics. Disruption of CYP2C9 activity by metabolic inhibition or pharmacogenetic variability underlies many of the adverse drug reactions that are associated with the enzyme. CYP2C9 is also the first human P450 to be crystallized, and the structural basis for its substrate and inhibitor selectivity is becoming increasingly clear. New, ultrapotent inhibitors of CYP2C9 have been synthesised that aid in the development of quantitative structure-activity relationship (QSAR) models to facilitate drug redesign, and extensive resequencing of the gene and studies of its regulation will undoubtedly help us understand interindividual variability in drug response and toxicity controlled by this enzyme.

scholarly journals Molecular modeling provides a structural basis for PERK inhibitor selectivity towards RIPK1

RSC Advances ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 367-375
Author(s):  
Chetan Chintha ◽  
Antonio Carlesso ◽  
Adrienne M. Gorman ◽  
Afshin Samali ◽  
Leif A. Eriksson
Keyword(s):  
Molecular Modeling ◽  
Molecular Modelling ◽  
Structural Basis ◽  
Inhibitor Selectivity

Molecular modelling explains the lack of selectivity for inhibitors GSK2606414 and GSK2656157, as compared to inhibitor AMG44.

scholarly journals Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone

2014 ◽  
Vol 70 (9) ◽  
pp. 1143-1149 ◽  
Author(s):  
Mika Aoyagi-Scharber ◽  
Anna S. Gardberg ◽  
Bryan K. Yip ◽  
Bing Wang ◽  
Yuqiao Shen ◽  
...  
Keyword(s):  
Binding Pocket ◽  
Clinical Development ◽  
Structural Basis ◽  
Water Molecules ◽  
The Novel ◽  
Breast Cancers ◽  
High Potency ◽  
Damage Response ◽  
Site Water ◽  
Inhibitor Selectivity

Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2), which are involved in DNA damage response, are targets of anticancer therapeutics. BMN 673 is a novel PARP1/2 inhibitor with substantially increased PARP-mediated tumor cytotoxicity and is now in later-stage clinical development for BRCA-deficient breast cancers. In co-crystal structures, BMN 673 is anchored to the nicotinamide-binding pocketviaan extensive network of hydrogen-bonding and π-stacking interactions, including those mediated by active-site water molecules. The novel di-branched scaffold of BMN 673 extends the binding interactions towards the outer edges of the pocket, which exhibit the least sequence homology among PARP enzymes. The crystallographic structural analyses reported here therefore not only provide critical insights into the molecular basis for the exceptionally high potency of the clinical development candidate BMN 673, but also new opportunities for increasing inhibitor selectivity.

scholarly journals Structural basis of inhibitor selectivity in MAP kinases

Structure ◽  
1998 ◽  
Vol 6 (9) ◽  
pp. 1117-1128 ◽  
Author(s):  
Zhulun Wang ◽  
Bertram J Canagarajah ◽  
Jeffrey C Boehm ◽  
Skouki Kassisà ◽  
Melanie H Cobb ◽  
...  
Keyword(s):  
Map Kinases ◽  
Structural Basis ◽  
Inhibitor Selectivity

scholarly journals Structural Basis of Inhibitor Selectivity in the BRD7/9 Subfamily of Bromodomains

2020 ◽  
Vol 63 (6) ◽  
pp. 3227-3237 ◽  
Author(s):  
Rezaul Md Karim ◽  
Alice Chan ◽  
Jin-Yi Zhu ◽  
Ernst Schönbrunn
Keyword(s):  
Structural Basis ◽  
Inhibitor Selectivity

The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor

2003 ◽  
Vol 11 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Benjamin E Turk ◽  
Thiang Yian Wong ◽  
Robert Schwarzenbacher ◽  
Emily T Jarrell ◽  
Stephen H Leppla ◽  
...  
Keyword(s):  
Lethal Factor ◽  
Structural Basis ◽  
Anthrax Lethal Factor ◽  
Inhibitor Selectivity

Structural Basis for Herbicidal Inhibitor Selectivity Revealed by Comparison of Crystal Structures of Plant and Mammalian 4-Hydroxyphenylpyruvate Dioxygenases‡

Biochemistry ◽  
2004 ◽  
Vol 43 (32) ◽  
pp. 10414-10423 ◽  
Author(s):  
Cheng Yang ◽  
James W. Pflugrath ◽  
Debra L. Camper ◽  
Mendy L. Foster ◽  
Daniel J. Pernich ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Structural Basis ◽  
Inhibitor Selectivity
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