The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Jeffrey W Bode - One of the best experts on this subject based on the ideXlab platform.

Adam Mccluskey - One of the best experts on this subject based on the ideXlab platform.

  • heterocyclic substituted cantharidin and norcantharidin analogues synthesis protein phosphatase 1 and 2a inhibition and anti cancer activity
    Bioorganic & Medicinal Chemistry Letters, 2007
    Co-Authors: Timothy A Hill, Scott G Stewart, Benjamin Sauer, Jayne Gilbert, Stephen P Ackland, Jennette A Sakoff, Adam Mccluskey
    Abstract:

    Norcantharidin (3) is a potent PP1 (IC(50)=9.0+/-1.4 microM) and PP2A (IC(50)=3.0+/-0.4 microM) inhibitor with 3-fold PP2A selectivity and induces growth inhibition (GI(50) approximately 45 microM) across a range of human cancer cell lines including those of colorectal (HT29, SW480), breast (MCF-7), ovarian (A2780), lung (H460), skin (A431), prostate (DU145), neuroblastoma (BE2-C), and glioblastoma (SJ-G2) origin. Until now limited modifications to the parent compound have been tolerated. Surprisingly, simple heterocyclic half-acid norcantharidin analogues are more active than the original lead compound, with the morphilino-substituted (9) being a more potent (IC(50)=2.8+/-0.10 microM) and selective (4.6-fold) PP2A inhibitor with greater in vitro cytotoxicity (GI(50) approximately 9.6 microM) relative to norcantharidin. The analogous thiomorpholine-substituted (10) displays increased PP1 inhibition (IC(50)=3.2+/-0 microM) and reduced PP2A inhibition (IC(50)=5.1+/-0.41 microM), to norcantharidin. Synthesis of the analogous cantharidin analogue (19) with incorporation of the amine nitrogen into the heterocycle further increases PP1 (IC(50)=5.9+/-2.2 microM) and PP2A (IC(50)=0.79+/-0.1 microM) inhibition and cell cytotoxicity (GI(50) approximately 3.3 microM). These analogues represent the most potent cantharidin analogues thus reported.

  • heterocyclic substituted cantharidin and norcantharidin analogues synthesis protein phosphatase 1 and 2a inhibition and anti cancer activity
    Bioorganic & Medicinal Chemistry Letters, 2007
    Co-Authors: Timothy A Hill, Scott G Stewart, Benjamin Sauer, Jayne Gilbert, Stephen P Ackland, Jennette A Sakoff, Adam Mccluskey
    Abstract:

    Norcantharidin (3) is a potent PP1 (IC50 = 9.0 +/- 1.4 mu M) and PP2A (IC50 = 3.0 +/- 0.4 mu M) inhibitor with 3-fold PP2A selectivity and induces growth inhibition (GI(50) similar to 45 mu M) across a range of human cancer cell lines including those of colorectal (HT29, SW480), breast (MCF-7), ovarian (A2780), lung (H460), skin (A431), prostate (DU145), neuroblastoma (BE2-C), and glioblastoma (SJ-G2) origin. Until now limited modifications to the parent compound have been tolerated. Surprisingly, simple heterocyclic half-acid norcantharidin analogues are more active than the original lead compound, with the morphilino-substituted (9) being a more potent (IC50 = 2.8 +/- 0.10 mu M) and selective (4.6-fold) PP2A inhibitor with greater in vitro cytotoxicity (GI(50) similar to 9.6 mu M) relative to norcantharidin. The analogous thiomorpholine-substituted (10) displays increased PP1 inhibition (IC50 = 3.2 +/- 0 mu M) and reduced PP2A inhibition (IC50 = 5.1 +/- 0.41 mu M), to norcantharidin. Synthesis of the analogous cantharidin analogue (19) with incorporation of the amine nitrogen into the heterocycle further increases PP1 (IC50 = 5.9 +/- 2.2 mu M) and PP2A (IC50 = 0.79 +/- 0.1 mu M) inhibition and cell cytotoxicity (GI(50) similar to 3.3 mu M). These analogues represent the most potent cantharidin analogues thus reported. Crown Copyright (c) 2007 Published by Elsevier Ltd. All rights reserved.

Gautam Panda - One of the best experts on this subject based on the ideXlab platform.

Timothy A Hill - One of the best experts on this subject based on the ideXlab platform.

  • heterocyclic substituted cantharidin and norcantharidin analogues synthesis protein phosphatase 1 and 2a inhibition and anti cancer activity
    Bioorganic & Medicinal Chemistry Letters, 2007
    Co-Authors: Timothy A Hill, Scott G Stewart, Benjamin Sauer, Jayne Gilbert, Stephen P Ackland, Jennette A Sakoff, Adam Mccluskey
    Abstract:

    Norcantharidin (3) is a potent PP1 (IC(50)=9.0+/-1.4 microM) and PP2A (IC(50)=3.0+/-0.4 microM) inhibitor with 3-fold PP2A selectivity and induces growth inhibition (GI(50) approximately 45 microM) across a range of human cancer cell lines including those of colorectal (HT29, SW480), breast (MCF-7), ovarian (A2780), lung (H460), skin (A431), prostate (DU145), neuroblastoma (BE2-C), and glioblastoma (SJ-G2) origin. Until now limited modifications to the parent compound have been tolerated. Surprisingly, simple heterocyclic half-acid norcantharidin analogues are more active than the original lead compound, with the morphilino-substituted (9) being a more potent (IC(50)=2.8+/-0.10 microM) and selective (4.6-fold) PP2A inhibitor with greater in vitro cytotoxicity (GI(50) approximately 9.6 microM) relative to norcantharidin. The analogous thiomorpholine-substituted (10) displays increased PP1 inhibition (IC(50)=3.2+/-0 microM) and reduced PP2A inhibition (IC(50)=5.1+/-0.41 microM), to norcantharidin. Synthesis of the analogous cantharidin analogue (19) with incorporation of the amine nitrogen into the heterocycle further increases PP1 (IC(50)=5.9+/-2.2 microM) and PP2A (IC(50)=0.79+/-0.1 microM) inhibition and cell cytotoxicity (GI(50) approximately 3.3 microM). These analogues represent the most potent cantharidin analogues thus reported.

  • heterocyclic substituted cantharidin and norcantharidin analogues synthesis protein phosphatase 1 and 2a inhibition and anti cancer activity
    Bioorganic & Medicinal Chemistry Letters, 2007
    Co-Authors: Timothy A Hill, Scott G Stewart, Benjamin Sauer, Jayne Gilbert, Stephen P Ackland, Jennette A Sakoff, Adam Mccluskey
    Abstract:

    Norcantharidin (3) is a potent PP1 (IC50 = 9.0 +/- 1.4 mu M) and PP2A (IC50 = 3.0 +/- 0.4 mu M) inhibitor with 3-fold PP2A selectivity and induces growth inhibition (GI(50) similar to 45 mu M) across a range of human cancer cell lines including those of colorectal (HT29, SW480), breast (MCF-7), ovarian (A2780), lung (H460), skin (A431), prostate (DU145), neuroblastoma (BE2-C), and glioblastoma (SJ-G2) origin. Until now limited modifications to the parent compound have been tolerated. Surprisingly, simple heterocyclic half-acid norcantharidin analogues are more active than the original lead compound, with the morphilino-substituted (9) being a more potent (IC50 = 2.8 +/- 0.10 mu M) and selective (4.6-fold) PP2A inhibitor with greater in vitro cytotoxicity (GI(50) similar to 9.6 mu M) relative to norcantharidin. The analogous thiomorpholine-substituted (10) displays increased PP1 inhibition (IC50 = 3.2 +/- 0 mu M) and reduced PP2A inhibition (IC50 = 5.1 +/- 0.41 mu M), to norcantharidin. Synthesis of the analogous cantharidin analogue (19) with incorporation of the amine nitrogen into the heterocycle further increases PP1 (IC50 = 5.9 +/- 2.2 mu M) and PP2A (IC50 = 0.79 +/- 0.1 mu M) inhibition and cell cytotoxicity (GI(50) similar to 3.3 mu M). These analogues represent the most potent cantharidin analogues thus reported. Crown Copyright (c) 2007 Published by Elsevier Ltd. All rights reserved.

Saurav Bera - One of the best experts on this subject based on the ideXlab platform.