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Related Concept Videos

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors

Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists

Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Pharmacokinetic–Pharmacodynamic Relationship: Problems01:24

Pharmacokinetic–Pharmacodynamic Relationship: Problems

The empirical approach to drug therapy optimization relies on correlating pharmacological response with administered dosage. Such an approach can be costly, time-consuming, and often yields poor correlation due to variables like formulation factors and drug elimination characteristics. A more precise approach correlates response with plasma drug concentration or the amount of drug in the body, rather than dosage. This is achieved through pharmacokinetic-pharmacodynamic (PK/PD) modeling, which...
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors01:20

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors

Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...

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Related Experiment Video

Updated: Jun 13, 2026

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

Is PDE4 too difficult a drug target?

Gerry Higgs

    Current Opinion in Investigational Drugs (London, England : 2000)
    |April 27, 2010
    PubMed
    Summary
    This summary is machine-generated.

    Selective phosphodiesterase 4 (PDE4) inhibitors show promise as anti-inflammatory drugs for conditions like asthma and COPD. Despite development challenges, new compounds offer potential therapeutic advancements.

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    Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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    Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

    Published on: October 26, 2015

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    Last Updated: Jun 13, 2026

    Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
    08:37

    Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

    Published on: November 5, 2014

    Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
    10:33

    Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

    Published on: October 26, 2015

    Area of Science:

    • Pharmacology
    • Drug Development
    • Inflammation Research

    Background:

    • The development of selective phosphodiesterase 4 (PDE4) inhibitors for anti-inflammatory purposes has been ongoing for over three decades.
    • While numerous PDE4 inhibitors have shown therapeutic potential in conditions such as asthma, COPD, atopic dermatitis, and psoriasis, none have yet achieved market approval.
    • A significant hurdle in PDE4 inhibitor development has been the occurrence of gastrointestinal adverse effects, notably nausea.

    Discussion:

    • Roflumilast has demonstrated significant therapeutic benefits in COPD patients, even at well-tolerated doses, indicating progress despite previous challenges.
    • Inhaled PDE4 inhibitor formulations, such as GSK's 256066 for asthma, and apremilast for psoriasis, are advancing through clinical trials.
    • These developments highlight the potential of PDE4 inhibitors as a novel class of anti-inflammatory agents.

    Key Insights:

    • Selective PDE4 inhibition remains a key strategy for novel anti-inflammatory drug discovery.
    • Overcoming gastrointestinal side effects is crucial for the successful clinical translation of PDE4 inhibitors.
    • Clinical successes with roflumilast, 256066, and apremilast underscore the therapeutic potential across various inflammatory diseases.

    Outlook:

    • Continued research and development are expected to yield approved PDE4 inhibitors for inflammatory conditions.
    • Future efforts will focus on optimizing efficacy while minimizing adverse effects for broader patient application.
    • The pipeline of PDE4 inhibitors suggests a promising future for this class of anti-inflammatory therapeutics.