Tags

Type your tag names separated by a space and hit enter

Monoclonal antibodies specific and inhibitory to human cytochromes P450 2C8, 2C9, and 2C19.
Drug Metab Dispos. 2001 Nov; 29(11):1410-23.DM

Abstract

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.

Authors+Show Affiliations

Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bldg. 37, Bethesda, MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11602516

Citation

Krausz, K W., et al. "Monoclonal Antibodies Specific and Inhibitory to Human Cytochromes P450 2C8, 2C9, and 2C19." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 29, no. 11, 2001, pp. 1410-23.
Krausz KW, Goldfarb I, Buters JT, et al. Monoclonal antibodies specific and inhibitory to human cytochromes P450 2C8, 2C9, and 2C19. Drug Metab Dispos. 2001;29(11):1410-23.
Krausz, K. W., Goldfarb, I., Buters, J. T., Yang, T. J., Gonzalez, F. J., & Gelboin, H. V. (2001). Monoclonal antibodies specific and inhibitory to human cytochromes P450 2C8, 2C9, and 2C19. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 29(11), 1410-23.
Krausz KW, et al. Monoclonal Antibodies Specific and Inhibitory to Human Cytochromes P450 2C8, 2C9, and 2C19. Drug Metab Dispos. 2001;29(11):1410-23. PubMed PMID: 11602516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Monoclonal antibodies specific and inhibitory to human cytochromes P450 2C8, 2C9, and 2C19. AU - Krausz,K W, AU - Goldfarb,I, AU - Buters,J T, AU - Yang,T J, AU - Gonzalez,F J, AU - Gelboin,H V, PY - 2001/10/17/pubmed PY - 2002/1/10/medline PY - 2001/10/17/entrez SP - 1410 EP - 23 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab Dispos VL - 29 IS - 11 N2 - 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. SN - 0090-9556 UR - https://www.unboundmedicine.com/medline/citation/11602516/Monoclonal_antibodies_specific_and_inhibitory_to_human_cytochromes_P450_2C8_2C9_and_2C19_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11602516 DB - PRIME DP - Unbound Medicine ER -