Selectivity of polycyclic inhibitors for human cytochrome P450s 1A1, 1A2, and 1B1.

  title={Selectivity of polycyclic inhibitors for human cytochrome P450s 1A1, 1A2, and 1B1.},
  author={Tsutomu Shimada and Hiroshi Yamazaki and Maryam Foroozesh and Nancy Eddy Hopkins and William L. Alworth and F. Peter Guengerich},
  journal={Chemical research in toxicology},
  volume={11 9},
Human cytochrome P450s 1A1, 1A2, and 1B1 are known to have overlapping substrate specificities. All are regulated in part by the Ah locus; P450 1A2 is expressed essentially only in liver, but P450s 1A1 and 1B1 are both expressed in many extrahepatic tissues. Twenty-five polycyclic hydrocarbons, many containing acetylenic side chains, were examined as inhibitors of the three enzymes using 7-ethoxyresorufin O-deethylation as the enzyme assay in all cases. Several compounds were inhibitory at low… 

Different mechanisms for inhibition of human cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic inhibitors.

Different mechanisms of inhibition of P450 1A1, 1A2, and 1B1 by PAHs and related chemicals are suggested and that interactions between P450 enzymes and PAH inhibitors are involved in differences in inhibition of the enzymes.

Potent inhibition of human cytochrome P450 1 enzymes by dimethoxyphenylvinyl thiophene

Investigation of the inhibitory effect of 2-[2-(3,5-dimethoxyphenyl)vinyl]-thiophene (DMPVT), produced from the chemical modification of oxyresveratrol, suggested DMPVT to be a strong noncompetitive inhibitor of human P450 1 enzymes that should be considered for a cancer chemopreventive agent in humans.

Mechanism-based inhibition of human cytochrome P450 1A1 by rhapontigenin.

The results suggest that rhapontigenin is a potent mechanism-based inactivator of human P450 1A1 and may be considered as a good candidate for a cancer chemopreventive agent in humans.

7-Ethynylcoumarins: selective inhibitors of human cytochrome P450s 1A1 and 1A2.

To discover new selective mechanism-based P450 inhibitors, eight 7-ethynylcoumarin derivatives were prepared through a facile two-step synthetic route, and 7E3M4PC with its two-plane structure fits into the P450 1A2's active site cavity with an orientation leading to no reactive binding, causing it to act as a competitive inhibitor.

New Selective Inhibitors of Cytochrome P450 2B4 and an Activator of Cytochrome P450 3A6 in Rabbit Liver Microsomes

The finding of a new activator of CYP3A6 having the structure quite different from that of CYp3A 6 activators known to date is reported, which is less effective inhibitors than parent compounds.

A new selective and potent inhibitor of human cytochrome P450 1B1 and its application to antimutagenesis.

TMS is selective for inhibiting P450 1B1 among other human P450s including 1A1, 1A2, and 3A4 and warrants consideration as a candidate for preventing mammary tumor formation by E(2) in humans.

Interaction of polycyclic aromatic hydrocarbons with human cytochrome P450 1B1 in inhibiting catalytic activity.

The results suggest that P450 1B1 interacts with synthetic polycyclic aromatic acetylenes and PAHs in different ways, depending on the chemicals, and that these differences in interactions may explain how these chemicals inhibit P450 activities by different mechanisms.


The results suggested that PMS is a potent and selective inhibitor of human P-450 1A1 and may be considered for use as a cancer chemopreventive agent in humans.