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Small Molecule

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Small Molecule - Free Register to Access Experts & Abstracts

Michael D. Cameron - One of the best experts on this subject based on the ideXlab platform.

  • Design of a Small Molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold–Small Molecule interactions
    Nature Chemistry, 2020
    Co-Authors: Hafeez S. Haniff, Laurent Knerr, Gogce Crynen, Jonas Boström, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Michael D. Cameron, Ilyas Yildirim
    Abstract:

    A selection-based screen has now revealed preferences in Small-Molecule chemotypes that bind RNA as well as preferences in the RNA motifs that bind Small Molecules. Analysis of these data enabled the design of a Small Molecule that selectively binds a non-coding microRNA and upregulates expression of vascular endothelial growth factor A. Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis in human endothelial cells, and increasing its expression is a potential treatment for heart failure. Here, we report the design of a Small Molecule (TGP-377) that specifically and potently enhances VEGFA expression by the targeting of a non-coding microRNA that regulates its expression. A selection-based screen, named two-dimensional combinatorial screening, revealed preferences in Small-Molecule chemotypes that bind RNA and preferences in the RNA motifs that bind Small Molecules. The screening program increased the dataset of known RNA motif–Small Molecule binding partners by 20-fold. Analysis of this dataset against the RNA-mediated pathways that regulate VEGFA defined that the microRNA-377 precursor, which represses Vegfa messenger RNA translation, is druggable in a selective manner. We designed TGP-377 to potently and specifically upregulate VEGFA in human umbilical vein endothelial cells. These studies illustrate the power of two-dimensional combinatorial screening to define molecular recognition events between ‘undruggable’ bioMolecules and Small Molecules, and the ability of sequence-based design to deliver efficacious structure-specific compounds.

  • Design of a Small Molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold–Small Molecule interactions
    Nature chemistry, 2020
    Co-Authors: Hafeez S. Haniff, Laurent Knerr, Gogce Crynen, Jonas Boström, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Xiaohui Liu, Michael D. Cameron
    Abstract:

    Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis in human endothelial cells, and increasing its expression is a potential treatment for heart failure. Here, we report the design of a Small Molecule (TGP-377) that specifically and potently enhances VEGFA expression by the targeting of a non-coding microRNA that regulates its expression. A selection-based screen, named two-dimensional combinatorial screening, revealed preferences in Small-Molecule chemotypes that bind RNA and preferences in the RNA motifs that bind Small Molecules. The screening program increased the dataset of known RNA motif-Small Molecule binding partners by 20-fold. Analysis of this dataset against the RNA-mediated pathways that regulate VEGFA defined that the microRNA-377 precursor, which represses Vegfa messenger RNA translation, is druggable in a selective manner. We designed TGP-377 to potently and specifically upregulate VEGFA in human umbilical vein endothelial cells. These studies illustrate the power of two-dimensional combinatorial screening to define molecular recognition events between 'undruggable' bioMolecules and Small Molecules, and the ability of sequence-based design to deliver efficacious structure-specific compounds.

Hafeez S. Haniff - One of the best experts on this subject based on the ideXlab platform.

  • Design of a Small Molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold–Small Molecule interactions
    Nature Chemistry, 2020
    Co-Authors: Hafeez S. Haniff, Laurent Knerr, Gogce Crynen, Jonas Boström, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Michael D. Cameron, Ilyas Yildirim
    Abstract:

    A selection-based screen has now revealed preferences in Small-Molecule chemotypes that bind RNA as well as preferences in the RNA motifs that bind Small Molecules. Analysis of these data enabled the design of a Small Molecule that selectively binds a non-coding microRNA and upregulates expression of vascular endothelial growth factor A. Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis in human endothelial cells, and increasing its expression is a potential treatment for heart failure. Here, we report the design of a Small Molecule (TGP-377) that specifically and potently enhances VEGFA expression by the targeting of a non-coding microRNA that regulates its expression. A selection-based screen, named two-dimensional combinatorial screening, revealed preferences in Small-Molecule chemotypes that bind RNA and preferences in the RNA motifs that bind Small Molecules. The screening program increased the dataset of known RNA motif–Small Molecule binding partners by 20-fold. Analysis of this dataset against the RNA-mediated pathways that regulate VEGFA defined that the microRNA-377 precursor, which represses Vegfa messenger RNA translation, is druggable in a selective manner. We designed TGP-377 to potently and specifically upregulate VEGFA in human umbilical vein endothelial cells. These studies illustrate the power of two-dimensional combinatorial screening to define molecular recognition events between ‘undruggable’ bioMolecules and Small Molecules, and the ability of sequence-based design to deliver efficacious structure-specific compounds.

  • Design of a Small Molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold–Small Molecule interactions
    Nature chemistry, 2020
    Co-Authors: Hafeez S. Haniff, Laurent Knerr, Gogce Crynen, Jonas Boström, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Xiaohui Liu, Michael D. Cameron
    Abstract:

    Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis in human endothelial cells, and increasing its expression is a potential treatment for heart failure. Here, we report the design of a Small Molecule (TGP-377) that specifically and potently enhances VEGFA expression by the targeting of a non-coding microRNA that regulates its expression. A selection-based screen, named two-dimensional combinatorial screening, revealed preferences in Small-Molecule chemotypes that bind RNA and preferences in the RNA motifs that bind Small Molecules. The screening program increased the dataset of known RNA motif-Small Molecule binding partners by 20-fold. Analysis of this dataset against the RNA-mediated pathways that regulate VEGFA defined that the microRNA-377 precursor, which represses Vegfa messenger RNA translation, is druggable in a selective manner. We designed TGP-377 to potently and specifically upregulate VEGFA in human umbilical vein endothelial cells. These studies illustrate the power of two-dimensional combinatorial screening to define molecular recognition events between 'undruggable' bioMolecules and Small Molecules, and the ability of sequence-based design to deliver efficacious structure-specific compounds.

  • Defining RNA–Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA
    ACS central science, 2017
    Co-Authors: Sai Pradeep Velagapudi, Hafeez S. Haniff, Yiling Luo, Tuan Tran, Yoshio Nakai, Mohammad Fallahi, Gustavo J. Martinez, Jessica L. Childs-disney, Matthew D. Disney
    Abstract:

    RNA drug targets are pervasive in cells, but methods to design Small Molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif–Small Molecule interactions identified via selection. Named High Throughput Structure–Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif–Small Molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a Small Molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the Small Molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cl...

Ilyas Yildirim - One of the best experts on this subject based on the ideXlab platform.

  • Design of a Small Molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold–Small Molecule interactions
    Nature Chemistry, 2020
    Co-Authors: Hafeez S. Haniff, Laurent Knerr, Gogce Crynen, Jonas Boström, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Michael D. Cameron, Ilyas Yildirim
    Abstract:

    A selection-based screen has now revealed preferences in Small-Molecule chemotypes that bind RNA as well as preferences in the RNA motifs that bind Small Molecules. Analysis of these data enabled the design of a Small Molecule that selectively binds a non-coding microRNA and upregulates expression of vascular endothelial growth factor A. Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis in human endothelial cells, and increasing its expression is a potential treatment for heart failure. Here, we report the design of a Small Molecule (TGP-377) that specifically and potently enhances VEGFA expression by the targeting of a non-coding microRNA that regulates its expression. A selection-based screen, named two-dimensional combinatorial screening, revealed preferences in Small-Molecule chemotypes that bind RNA and preferences in the RNA motifs that bind Small Molecules. The screening program increased the dataset of known RNA motif–Small Molecule binding partners by 20-fold. Analysis of this dataset against the RNA-mediated pathways that regulate VEGFA defined that the microRNA-377 precursor, which represses Vegfa messenger RNA translation, is druggable in a selective manner. We designed TGP-377 to potently and specifically upregulate VEGFA in human umbilical vein endothelial cells. These studies illustrate the power of two-dimensional combinatorial screening to define molecular recognition events between ‘undruggable’ bioMolecules and Small Molecules, and the ability of sequence-based design to deliver efficacious structure-specific compounds.

Laurent Knerr - One of the best experts on this subject based on the ideXlab platform.

  • Design of a Small Molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold–Small Molecule interactions
    Nature Chemistry, 2020
    Co-Authors: Hafeez S. Haniff, Laurent Knerr, Gogce Crynen, Jonas Boström, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Michael D. Cameron, Ilyas Yildirim
    Abstract:

    A selection-based screen has now revealed preferences in Small-Molecule chemotypes that bind RNA as well as preferences in the RNA motifs that bind Small Molecules. Analysis of these data enabled the design of a Small Molecule that selectively binds a non-coding microRNA and upregulates expression of vascular endothelial growth factor A. Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis in human endothelial cells, and increasing its expression is a potential treatment for heart failure. Here, we report the design of a Small Molecule (TGP-377) that specifically and potently enhances VEGFA expression by the targeting of a non-coding microRNA that regulates its expression. A selection-based screen, named two-dimensional combinatorial screening, revealed preferences in Small-Molecule chemotypes that bind RNA and preferences in the RNA motifs that bind Small Molecules. The screening program increased the dataset of known RNA motif–Small Molecule binding partners by 20-fold. Analysis of this dataset against the RNA-mediated pathways that regulate VEGFA defined that the microRNA-377 precursor, which represses Vegfa messenger RNA translation, is druggable in a selective manner. We designed TGP-377 to potently and specifically upregulate VEGFA in human umbilical vein endothelial cells. These studies illustrate the power of two-dimensional combinatorial screening to define molecular recognition events between ‘undruggable’ bioMolecules and Small Molecules, and the ability of sequence-based design to deliver efficacious structure-specific compounds.

  • Design of a Small Molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold–Small Molecule interactions
    Nature chemistry, 2020
    Co-Authors: Hafeez S. Haniff, Laurent Knerr, Gogce Crynen, Jonas Boström, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Xiaohui Liu, Michael D. Cameron
    Abstract:

    Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis in human endothelial cells, and increasing its expression is a potential treatment for heart failure. Here, we report the design of a Small Molecule (TGP-377) that specifically and potently enhances VEGFA expression by the targeting of a non-coding microRNA that regulates its expression. A selection-based screen, named two-dimensional combinatorial screening, revealed preferences in Small-Molecule chemotypes that bind RNA and preferences in the RNA motifs that bind Small Molecules. The screening program increased the dataset of known RNA motif-Small Molecule binding partners by 20-fold. Analysis of this dataset against the RNA-mediated pathways that regulate VEGFA defined that the microRNA-377 precursor, which represses Vegfa messenger RNA translation, is druggable in a selective manner. We designed TGP-377 to potently and specifically upregulate VEGFA in human umbilical vein endothelial cells. These studies illustrate the power of two-dimensional combinatorial screening to define molecular recognition events between 'undruggable' bioMolecules and Small Molecules, and the ability of sequence-based design to deliver efficacious structure-specific compounds.

Gogce Crynen - One of the best experts on this subject based on the ideXlab platform.

  • Design of a Small Molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold–Small Molecule interactions
    Nature Chemistry, 2020
    Co-Authors: Hafeez S. Haniff, Laurent Knerr, Gogce Crynen, Jonas Boström, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Michael D. Cameron, Ilyas Yildirim
    Abstract:

    A selection-based screen has now revealed preferences in Small-Molecule chemotypes that bind RNA as well as preferences in the RNA motifs that bind Small Molecules. Analysis of these data enabled the design of a Small Molecule that selectively binds a non-coding microRNA and upregulates expression of vascular endothelial growth factor A. Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis in human endothelial cells, and increasing its expression is a potential treatment for heart failure. Here, we report the design of a Small Molecule (TGP-377) that specifically and potently enhances VEGFA expression by the targeting of a non-coding microRNA that regulates its expression. A selection-based screen, named two-dimensional combinatorial screening, revealed preferences in Small-Molecule chemotypes that bind RNA and preferences in the RNA motifs that bind Small Molecules. The screening program increased the dataset of known RNA motif–Small Molecule binding partners by 20-fold. Analysis of this dataset against the RNA-mediated pathways that regulate VEGFA defined that the microRNA-377 precursor, which represses Vegfa messenger RNA translation, is druggable in a selective manner. We designed TGP-377 to potently and specifically upregulate VEGFA in human umbilical vein endothelial cells. These studies illustrate the power of two-dimensional combinatorial screening to define molecular recognition events between ‘undruggable’ bioMolecules and Small Molecules, and the ability of sequence-based design to deliver efficacious structure-specific compounds.

  • Design of a Small Molecule that stimulates vascular endothelial growth factor A enabled by screening RNA fold–Small Molecule interactions
    Nature chemistry, 2020
    Co-Authors: Hafeez S. Haniff, Laurent Knerr, Gogce Crynen, Jonas Boström, Daniel Abegg, Alexander Adibekian, Elizabeth Lekah, Kye Won Wang, Xiaohui Liu, Michael D. Cameron
    Abstract:

    Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis in human endothelial cells, and increasing its expression is a potential treatment for heart failure. Here, we report the design of a Small Molecule (TGP-377) that specifically and potently enhances VEGFA expression by the targeting of a non-coding microRNA that regulates its expression. A selection-based screen, named two-dimensional combinatorial screening, revealed preferences in Small-Molecule chemotypes that bind RNA and preferences in the RNA motifs that bind Small Molecules. The screening program increased the dataset of known RNA motif-Small Molecule binding partners by 20-fold. Analysis of this dataset against the RNA-mediated pathways that regulate VEGFA defined that the microRNA-377 precursor, which represses Vegfa messenger RNA translation, is druggable in a selective manner. We designed TGP-377 to potently and specifically upregulate VEGFA in human umbilical vein endothelial cells. These studies illustrate the power of two-dimensional combinatorial screening to define molecular recognition events between 'undruggable' bioMolecules and Small Molecules, and the ability of sequence-based design to deliver efficacious structure-specific compounds.