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An. R. Acad. Nac. Farm., 2007, 73: 703-724

Artículo original

Are adrenomedullin positive modulators novel
matrix metalloproteinase inhibitors?

Recibido el 28 de marzo de 2007

MARIO A. GARCÍA, SONSOLES MARTÍN-SANTAMARÍA,
ANA RAMOS, BEATRIZ DE PASCUAL-TERESA *
Departamento de Química. Facultad de Farmacia,

Universidad San Pablo CEU, Urbanización Montepríncipe,
28668-Boadilla del Monte, Madrid (Spain)

ABSTRACT

Matrix metalloproteinases (MMPs), are a family of structurally related zinc
containing enzymes that play a major role in the breakdown of connective tissue
and therefore, are targets for therapeutic inhibitors in many inflammatory,
malignant, and degenerative diseases. On the other hand, it has been recently
demonstrated that one of these enzymes, MMP-2, a type IV collagenase, termed
gelatinase A, cleaves the angiogenic peptide adrenomedullin (AM) (1). AM is a
peptide hormone that plays a critical role in several diseases such as diabetes,
hypertension and cancer. In a High Throughput Screening (HTS) carried out at the
National Cancer Institute (NCI), a series of AM modulators were identified, with an
interesting hypotensive activity (2). In order to shed light into the mechanism of
action of these interesting compounds, we have hypothesized that they may be

* Beatriz de Pascual-Teresa.
Facultad de Farmacia. Universidad San Pablo CEU.
Ctra. Boadilla del Monte, km. 5,300. Boadilla del Monte. Madrid.
Phone: +34913724796. Fax: +34913724009 bpaster@ceu.es
Sonsoles Martín-Santamaría.
Facultad de Farmacia. Universidad San Pablo CEU.
Ctra. Boadilla del Monte, km. 5,300. Boadilla del Monte. Madrid.
Phone: +34913724798 Fax: +34913724009 smar.fcex@ceu.es
Abbreviations: MMPs: Matrix metalloproteinases; AM: adrenomedullin; HTS: High
Throughput Screening; NCI: National Cancer Institute.

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