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Inhibitory and non-inhibitory monoclonal antibodies to human cytochrome P450 3A3/4.
Biochem Pharmacol. 1995 Nov 27; 50(11):1841-50.BP

Abstract

Cytochromes P450 3A3/4 are inordinately important P450 enzymes catalyzing the metabolism of a large variety of clinically useful drugs, steroids, and carcinogens. Two monoclonal antibodies, MAb 3-29-9 and MAb 275-1-2, were prepared to human P450 3A4 from mice immunized with baculovirus-expressed human P450 3A4. MAb 3-29-9 was a powerful inhibitor of the enzymatic activity of P450 3A3/4/5. MAb 3-29-9 inhibited the P450 3A3, 3A4, and 3A5 catalyzed metabolism of substrates of divergent molecular weights, e.g., p-nitroanisole, phenanthrene, diazepam, testosterone, taxol, and cyclosporin. However, MAb 3-29-9 did not give a western blot with P450 3A3 or 3A4. MAb 275-1-2 was non-inhibitory but yielded a strong western blot with P450 3A3 and 3A4 but not with 3A5, and thus distinguished between 3A3/4 and 3A5. The two MAbs did not cross-react with human 2E1, 1A2, 2B6, 2C8, and 2C9; rat 2A1, 3A1/2, 4A1, 4A3, and 2B1; and mouse 1A1 and 1A2. MAb 3-29-9 has been used successfully to measure the quantitative contribution of P450 3A3 and 3A4 to the metabolism of the above-designated substrates in human adult liver. MAb 3-29-9 and MAb 275-1-2 are precise and sensitive reagents for P450 3A studies.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8615863

Citation

Gelboin, H V., et al. "Inhibitory and Non-inhibitory Monoclonal Antibodies to Human Cytochrome P450 3A3/4." Biochemical Pharmacology, vol. 50, no. 11, 1995, pp. 1841-50.
Gelboin HV, Krausz KW, Goldfarb I, et al. Inhibitory and non-inhibitory monoclonal antibodies to human cytochrome P450 3A3/4. Biochem Pharmacol. 1995;50(11):1841-50.
Gelboin, H. V., Krausz, K. W., Goldfarb, I., Buters, J. T., Yang, S. K., Gonzalez, F. J., Korzekwa, K. R., & Shou, M. (1995). Inhibitory and non-inhibitory monoclonal antibodies to human cytochrome P450 3A3/4. Biochemical Pharmacology, 50(11), 1841-50.
Gelboin HV, et al. Inhibitory and Non-inhibitory Monoclonal Antibodies to Human Cytochrome P450 3A3/4. Biochem Pharmacol. 1995 Nov 27;50(11):1841-50. PubMed PMID: 8615863.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitory and non-inhibitory monoclonal antibodies to human cytochrome P450 3A3/4. AU - Gelboin,H V, AU - Krausz,K W, AU - Goldfarb,I, AU - Buters,J T, AU - Yang,S K, AU - Gonzalez,F J, AU - Korzekwa,K R, AU - Shou,M, PY - 1995/11/27/pubmed PY - 1995/11/27/medline PY - 1995/11/27/entrez SP - 1841 EP - 50 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 50 IS - 11 N2 - Cytochromes P450 3A3/4 are inordinately important P450 enzymes catalyzing the metabolism of a large variety of clinically useful drugs, steroids, and carcinogens. Two monoclonal antibodies, MAb 3-29-9 and MAb 275-1-2, were prepared to human P450 3A4 from mice immunized with baculovirus-expressed human P450 3A4. MAb 3-29-9 was a powerful inhibitor of the enzymatic activity of P450 3A3/4/5. MAb 3-29-9 inhibited the P450 3A3, 3A4, and 3A5 catalyzed metabolism of substrates of divergent molecular weights, e.g., p-nitroanisole, phenanthrene, diazepam, testosterone, taxol, and cyclosporin. However, MAb 3-29-9 did not give a western blot with P450 3A3 or 3A4. MAb 275-1-2 was non-inhibitory but yielded a strong western blot with P450 3A3 and 3A4 but not with 3A5, and thus distinguished between 3A3/4 and 3A5. The two MAbs did not cross-react with human 2E1, 1A2, 2B6, 2C8, and 2C9; rat 2A1, 3A1/2, 4A1, 4A3, and 2B1; and mouse 1A1 and 1A2. MAb 3-29-9 has been used successfully to measure the quantitative contribution of P450 3A3 and 3A4 to the metabolism of the above-designated substrates in human adult liver. MAb 3-29-9 and MAb 275-1-2 are precise and sensitive reagents for P450 3A studies. SN - 0006-2952 UR - https://www.unboundmedicine.com/medline/citation/8615863/Inhibitory_and_non_inhibitory_monoclonal_antibodies_to_human_cytochrome_P450_3A3/4_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0006-2952(95)02077-2 DB - PRIME DP - Unbound Medicine ER -