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Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
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Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
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Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
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Lipids as Anchors01:32

Lipids as Anchors

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In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
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cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

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Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
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Related Experiment Video

Updated: Jun 8, 2025

Detection of Protein Palmitoylation in Cultured Hippocampal Neurons by Immunoprecipitation and Acyl-Biotin Exchange ABE
16:33

Detection of Protein Palmitoylation in Cultured Hippocampal Neurons by Immunoprecipitation and Acyl-Biotin Exchange ABE

Published on: February 18, 2013

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Pan-Transcriptional Enhanced Associated Domain Palmitoylation Pocket Covalent Inhibitor.

Jinhyuk Kim1,2, Hadong Kim2, Jongwan Kim3,4

  • 1The Interdisciplinary Graduate Program in Integrative Biotechnology & Translational Medicine, Yonsei University, Incheon 21983, Republic of Korea.

Journal of Medicinal Chemistry
|November 2, 2024
PubMed
Summary

Researchers developed a new drug targeting the Hippo-TEAD pathway to treat cancers. Compound 3 is a potent, orally available inhibitor of TEAD proteins, offering a promising therapeutic strategy.

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Acyl-PEGyl Exchange Gel Shift Assay for Quantitative Determination of Palmitoylation of Brain Membrane Proteins

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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

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Related Experiment Videos

Last Updated: Jun 8, 2025

Detection of Protein Palmitoylation in Cultured Hippocampal Neurons by Immunoprecipitation and Acyl-Biotin Exchange ABE
16:33

Detection of Protein Palmitoylation in Cultured Hippocampal Neurons by Immunoprecipitation and Acyl-Biotin Exchange ABE

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Acyl-PEGyl Exchange Gel Shift Assay for Quantitative Determination of Palmitoylation of Brain Membrane Proteins
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Acyl-PEGyl Exchange Gel Shift Assay for Quantitative Determination of Palmitoylation of Brain Membrane Proteins

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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

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Area of Science:

  • Molecular Biology
  • Oncology
  • Drug Discovery

Background:

  • The Hippo signaling pathway regulates organ size and is implicated in cancer.
  • Transcriptional Enhanced Associated Domain (TEAD) proteins are key mediators in this pathway.
  • Palmitoylation of TEAD proteins is crucial for their oncogenic activity, making it a therapeutic target.

Purpose of the Study:

  • To develop novel inhibitors targeting TEAD palmitoylation sites.
  • To identify potent and orally bioavailable covalent pan-TEAD inhibitors for cancer therapy.

Main Methods:

  • Structure-based drug design utilizing insights from K-975.
  • Iterative optimization of hit compounds to enhance potency and pharmacokinetic properties.
  • Evaluation of inhibitor activity against TEAD proteins.

Main Results:

  • Compound 1 was identified as an initial hit through structure-based design.
  • Optimization led to the development of Compound 3, a potent covalent pan-TEAD inhibitor.
  • Compound 3 demonstrated high potency and favorable oral bioavailability.

Conclusions:

  • Targeting TEAD palmitoylation is a viable strategy for treating TEAD-dependent cancers.
  • Compound 3 represents a promising drug candidate for further development in oncology.
  • The developed inhibitor effectively targets multiple TEAD proteins, offering broad therapeutic potential.