DMD Simcyp

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Krausz, K. W.
Right arrow Articles by Gelboin, H. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Krausz, K. W.
Right arrow Articles by Gelboin, H. V.

Vol. 29, Issue 11, 1410-1423, November 2001

Monoclonal Antibodies Specific and Inhibitory to Human Cytochromes P450 2C8, 2C9, and 2C19

Kristopher W. Krausz, Inna Goldfarb, Jeroen T. M. Buters,1 Tian J. Yang,2 Frank J. Gonzalez, and Harry V. Gelboin

Laboratory of Molecular Carcinogenesis and Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Hybridomas were isolated that produce 13 monoclonal antibodies (mAbs) that are specific and highly inhibitory to members of the human P450 2C subfamily, 2C8, 2C9, 2C9*2, and 2C19. Many of the mAbs to P450 2C8, 2C9, and 2C19 are specific and exhibit potent inhibitory activity (85-95%). mAb 281-1-1 specifically binds, immunoblots, and strongly inhibits the activity of P450 2C8. mAb 763-15-5 specifically binds and strongly inhibits the activity of P450 2C9. mAb 1-7-4-8 specifically binds and strongly inhibits the activity of P450 2C19. The other mAbs bind and inhibit sets and subsets of the P450 2C family. The single and the combinatorial use of the mAbs can "reaction phenotype", i.e., determine the metabolic contribution and interindividual variation of a P450 isoform for the metabolism of a drug or nondrug xenobiotic in human liver microsomes. The utility of the mAb-based analytic system was examined with the model substrates Taxol (paclitaxel), diazepam, tolbutamide, diclofenac, mephenytoin, and imipramine. The mAb system can identify drugs metabolized by a common P450 or several P450s and polymorphic P450s. The mAb system identifies drugs or drug metabolic pathways that are catalyzed by a single P450 and thus may be used for in vivo phenotyping. The mAb system can identify whether a particular drug is metabolized by a single P450 that may exhibit polymorphic expression in humans. The mAb system offers large potential for studies of cytochrome P450 function useful in drug discovery and reduces the possibility of adverse drug reactions due to polymorphisms and drug interactions.


1 Current address: Institute for Toxicol-GSF, Oberschleisschim, Germany.

2 Current address: DuPont Pharmaceuticals Co., Newark, Delaware.


Copyright © 2001 by U.S. Government



This article has been cited by other articles:


Home page
Drug Metab. Dispos.Home page
M. Shou and A. Y. H. Lu
Antibodies as a Probe in Cytochrome P450 Research
Drug Metab. Dispos., May 1, 2009; 37(5): 925 - 931.
[Abstract] [Full Text] [PDF]


Home page
Drug Metab. Dispos.Home page
S.-Y. Chang, W. Li, S. C. Traeger, B. Wang, D. Cui, H. Zhang, B. Wen, and A. D. Rodrigues
Confirmation That Cytochrome P450 2C8 (CYP2C8) Plays a Minor Role in (S)-(+)- and (R)-(-)-Ibuprofen Hydroxylation in Vitro
Drug Metab. Dispos., December 1, 2008; 36(12): 2513 - 2522.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
T. K. L. Kiang, P. C. Ho, M. R. Anari, V. Tong, F. S. Abbott, and T. K. H. Chang
Contribution of CYP2C9, CYP2A6, and CYP2B6 to Valproic Acid Metabolism in Hepatic Microsomes from Individuals with the CYP2C9*1/*1 Genotype
Toxicol. Sci., December 1, 2006; 94(2): 261 - 271.
[Abstract] [Full Text] [PDF]


Home page
Drug Metab. Dispos.Home page
L. D. Stuchal, K. M. Kleinow, J. J. Stegeman, and M. O. James
DEMETHYLATION OF THE PESTICIDE METHOXYCHLOR IN LIVER AND INTESTINE FROM UNTREATED, METHOXYCHLOR-TREATED, AND 3-METHYLCHOLANTHRENE-TREATED CHANNEL CATFISH (ICTALURUS PUNCTATUS): EVIDENCE FOR ROLES OF CYP1 AND CYP3A FAMILY ISOZYMES
Drug Metab. Dispos., June 1, 2006; 34(6): 932 - 938.
[Abstract] [Full Text] [PDF]


Home page
Drug Metab. Dispos.Home page
Y. Chang, D. E. Moody, and E. F. McCance-Katz
NOVEL METABOLITES OF BUPRENORPHINE DETECTED IN HUMAN LIVER MICROSOMES AND HUMAN URINE
Drug Metab. Dispos., March 1, 2006; 34(3): 440 - 448.
[Abstract] [Full Text] [PDF]


Home page
J Clin PharmacolHome page
H. V. Gelboin and K. Krausz
Monoclonal antibodies and multifunctional cytochrome p450: drug metabolism as paradigm.
J. Clin. Pharmacol., March 1, 2006; 46(3): 353 - 372.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
L. Quintieri, C. Geroni, M. Fantin, R. Battaglia, A. Rosato, W. Speed, P. Zanovello, and M. Floreani
Formation and Antitumor Activity of PNU-159682, A Major Metabolite of Nemorubicin in Human Liver Microsomes
Clin. Cancer Res., February 15, 2005; 11(4): 1608 - 1617.
[Abstract] [Full Text] [PDF]


Home page
Drug Metab. Dispos.Home page
V. N. Hirani, J. L. Raucy, and J. M. Lasker
CONVERSION OF THE HIV PROTEASE INHIBITOR NELFINAVIR TO A BIOACTIVE METABOLITE BY HUMAN LIVER CYP2C19
Drug Metab. Dispos., December 1, 2004; 32(12): 1462 - 1467.
[Abstract] [Full Text] [PDF]


Home page
Drug Metab. Dispos.Home page
B. Wang, R. I. Sanchez, R. B. Franklin, D. C. Evans, and S.-E. W. Huskey
THE INVOLVEMENT OF CYP3A4 AND CYP2C9 IN THE METABOLISM OF 17{alpha}-ETHINYLESTRADIOL
Drug Metab. Dispos., November 1, 2004; 32(11): 1209 - 1212.
[Abstract] [Full Text] [PDF]


Home page
Drug Metab. Dispos.Home page
X. Cai, R. W. Wang, R. W. Edom, D. C. Evans, M. Shou, A. D. Rodrigues, W. Liu, D. C. Dean, and T. A. Baillie
VALIDATION OF (-)-N-3-BENZYL-PHENOBARBITAL AS A SELECTIVE INHIBITOR OF CYP2C19 IN HUMAN LIVER MICROSOMES
Drug Metab. Dispos., June 1, 2004; 32(6): 584 - 586.
[Abstract] [Full Text] [PDF]


Home page
Drug Metab. Dispos.Home page
M. Hu, K. Krausz, J. Chen, X. Ge, J. Li, H. L. Gelboin, and Frank. J. Gonzalez
IDENTIFICATION OF CYP1A2 AS THE MAIN ISOFORM FOR THE PHASE I HYDROXYLATED METABOLISM OF GENISTEIN AND A PRODRUG CONVERTING ENZYME OF METHYLATED ISOFLAVONES
Drug Metab. Dispos., July 1, 2003; 31(7): 924 - 931.
[Abstract] [Full Text] [PDF]


Home page
Drug Metab. Dispos.Home page
A. Y. H. Lu, R. W. Wang, and J. H. Lin
Cytochrome P450 In Vitro Reaction Phenotyping: A Re-evaluation of Approaches Used for P450 Isoform Identification
Drug Metab. Dispos., April 1, 2003; 31(4): 345 - 350.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
A.-M. Yu, J. R. Idle, K. W. Krausz, A. Kupfer, and F. J. Gonzalez
Contribution of Individual Cytochrome P450 Isozymes to the O-Demethylation of the Psychotropic beta -Carboline Alkaloids Harmaline and Harmine
J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 315 - 322.
[Abstract] [Full Text]




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
 Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics.