X-ray Crystal Structures of Escherichia coli RNA Polymerase with Switch Region Binding Inhibitors Enable Rational Design of Squaramides with an Improved Fraction Unbound to Human Plasma Protein

Journal of Medicinal Chemistry

Volumn 58, Issue 7, 2015, Pages 3156-3171

  Molodtsov, Vadim ^a   Fleming, Paul R ^b   Eyermann, Charles J ^b   Ferguson, Andrew D ^b   Foulk, Melinda A ^b   McKinney, David C ^b   Masse, Craig E ^c   Buurman, Ed T ^b   Murakami, Katsuhiko S ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

^b ASTRAZENECA   (United Kingdom)

^c Nimbus Therapeutics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MYXOPYRONIN; NATURAL PRODUCT; NUCLEOTIDYLTRANSFERASE INHIBITOR; PIPERIDINE; PLASMA PROTEIN; RNA POLYMERASE; SQUARAMIDE; UNCLASSIFIED DRUG; DNA DIRECTED RNA POLYMERASE; ENZYME INHIBITOR; ESCHERICHIA COLI PROTEIN; LACTONE; MYXOPYRONIN A; MYXOPYRONIN B; RNA POLYMERASE ALPHA SUBUNIT; RPOB PROTEIN, E COLI;

ANTIMICROBIAL ACTIVITY; ARTICLE; BINDING AFFINITY; BIOCHEMICAL COMPOSITION; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; DNA TEMPLATE; DRUG POTENCY; ESCHERICHIA COLI; HAEMOPHILUS INFLUENZAE; HYDROPHOBICITY; IN VITRO STUDY; NONHUMAN; X RAY; ANTAGONISTS AND INHIBITORS; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; DRUG EFFECTS; GENETICS; HIGH THROUGHPUT SCREENING; HUMAN; METABOLISM; PROTEIN CONFORMATION; STRUCTURE ACTIVITY RELATION; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

BINDING SITES; BLOOD PROTEINS; CHEMISTRY TECHNIQUES, SYNTHETIC; CRYSTALLOGRAPHY, X-RAY; DNA-DIRECTED RNA POLYMERASES; DRUG DESIGN; ENZYME INHIBITORS; ESCHERICHIA COLI PROTEINS; HAEMOPHILUS INFLUENZAE; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; LACTONES; MODELS, MOLECULAR; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84927637546     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00050     Document Type: Article

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