Noncovalent forces, other than hydrophobic interactions, are important determinants of substrate bias exhibited by some cytochromes P450. The CYP2C9 pharmacophore is proposed to include either an anionic group or hydrogen bond donor in addition to its hydrophobic groups. By constructing analogs of benzbromarone, evidence supporting the existence of a 2C9 anion-binding site was revealed. A nonsubstituted phenol analog was determined to have a pKa of 8.4 and a Ki of 414 nM whereas those with dihalogenated benzoyl phenols had pKa values between 4.2 to 5.2 and Ki values as low as 1 nM. The nonhalogenated, nonionizable analog is the poorest binder at 796 nM. The Ki range covers around three orders of magnitude with even the weakest binder being a more potent inhibitor than 2C9 substrate phenytoin. Thus, benzbromarone derivatives represent a class of molecules with the potential to reveal more structural details of the 2C9 active site.
Pharmacology, Toxicology and Pharmaceutical Science
2
11%
Medicine and Dentistry
2
11%
Chemistry
2
11%
Other
1
6%
Unknown
5
28%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 February 2013.
All research outputs
#7,405,506
of 34,054,827 outputs
Outputs from Drug Metabolism and Disposition
#711
of 4,052 outputs
Outputs of similar age
#17,516
of 75,289 outputs
Outputs of similar age from Drug Metabolism and Disposition
#11
of 26 outputs
Altmetric has tracked 34,054,827 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 4,052 research outputs from this source. They receive a mean Attention Score of 4.8. This one has gotten more attention than average, scoring higher than 69% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 75,289 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
