CYP19A1 binds Aromatase inhibitors

Stable Identifier
R-HSA-9707353
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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CYP19A1 (aromatase) is the enzyme that catalyses a key aromatization step in the synthesis of estrogens from androgens. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase (Brodie et al. 1981). Many breast cancers are hormone receptor-positive, meaning their growth is stimulated and/or maintained by the presence of hormones such as estrogen or progesterone. In postmenopausal women, estrogen is primarily derived from the aromatization of adrenally-produced androgens into estrogens by CYP19A1. Aromatase inhibitors are a class of drugs used in the treatment of breast cancer in postmenopausal women by competitively inhibiting CYP19A1. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing growth of hormone receptor-positive breast tumours (Chumsri et al. 2011). Aromatase inhibitors can be first-generation (e.g. aminoglutethimide) (Greco et al. 2005), second-generation (e.g. fadrozole) (Browne et al. 1991), and third-generation (e.g. anastrozole, letrozole, and exemestane) (Bhatnagar et al. 1990, Cohen et al. 2002, Buzdar et al. 2002) agents. They can also be divided into type I and type II inhibitors. Type I inhibitors have a steroidal structure similar to androgens and inactivate CYP19A1 irreversibly by blocking the substrate-binding site, and are therefore known as aromatase inactivators. Type II inhibitors are nonsteroidal and their action is reversible.
Literature References
PubMed ID Title Journal Year
1825337 Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease

Gude, C, Steele, RE, Bhatnager, A, Rodriguez, H, Browne, LJ

J Med Chem 1991
16332571 HPMA copolymer-aminoglutethimide conjugates inhibit aromatase in MCF-7 cell lines

Penning, NA, Greco, F, Nicholson, RI, Vicent, MJ, Duncan, R

J Drug Target 2005
12404296 An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane

Nabholtz, JM, Robertson, JF, Buzdar, AU, Eiermann, W

Cancer 2002
2149502 Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor

Schieweck, K, Bowman, R, Häusler, A, Bhatnagar, AS, Lang, M

J Steroid Biochem Mol Biol 1990
7336466 Inactivation of aromatase in vitro by 4-hydroxy-4-androstene-3,17-dione and 4-acetoxy-4-androstene-3,17-dione and sustained effects in vivo

Robinson, CH, Brodie, AM, Marcotte, PA, Garrett, WM, Hendrickson, JR, Tsai-Morris, CH

Steroids 1981
11895893 Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer

Cohen, MH, Li, N, Pazdur, R, Chen, G, Johnson, JR

Clin Cancer Res 2002
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