MMP12→Matrix Metalloproteinase 1→Isoquinolines→Nuclear Proteins→poly-ADP-ribose

• 19703773(MMP12): The identification of beta-hydroxy carboxylic acids as selective MMP-12 inhibitors.

  A new class of selective MMP-12 inhibitors have been identified via high throughput screening.

• 10406637(Matrix Metalloproteinase 1): Synthesis and identification of conformationally constrained selective MMP inhibitors.

  We have discovered a new series of potent conformationally constrained MMP Inhibitors that are selective for MMP-13 over MMP-1.

• 18409175(Isoquinolines): On the way to selective PARP-2 inhibitors. Design, synthesis, and preliminary evaluation of a series of isoquinolinone derivatives.

  Among them , we identified the 5-benzoyloxyisoquinolin-1 (2 H) - one derivative as the most selective PARP-2 inhibitor reported so far , with a PARP-2 / PARP-1 selectivity index greater than 60.

• 10364231(Nuclear Proteins): PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase.

  We propose to call this enzyme poly (ADP-ribose) polymerase 2 (PARP-2).

• 3080986(poly-ADP-ribose): Metabolic consequences of DNA damage: DNA damage induces alterations in glucose metabolism by activation of poly (ADP-ribose) polymerase.

  In this communication we show that activation of poly (ADP-ribose) polymerase by DNA damage can produce drastic alterations in carbohydrate metabolism.