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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
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[Inhibitors of PCSK9].

Iveta Petrova-Slater1, Andrea Denegri2, Elena Pasotti2

  • 1Cardiocentro Ticino, Servizio ricerca cardiovascolare, Via Tesserete 48, 6900 Lugano.

Revue Medicale Suisse
|July 21, 2017
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Summary
This summary is machine-generated.

New PCSK9 inhibitor drugs offer a promising approach to further reduce cardiovascular disease (CVD) risk in patients with high low-density lipoprotein cholesterol (LDL-C) who do not benefit enough from statins.

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Area of Science:

  • Cardiovascular medicine
  • Lipidology
  • Pharmacology

Background:

  • Elevated low-density lipoprotein cholesterol (LDL-C) is strongly associated with cardiovascular disease (CVD).
  • Statins effectively lower LDL-C but may cause side effects and leave residual CVD risk.
  • Significant residual risk persists in patients undergoing statin therapy for CVD prevention.

Purpose of the Study:

  • To review the mechanism of action of proprotein convertase subtilisin kexin 9 (PCSK9) antibodies.
  • To discuss the safety and efficacy of PCSK9 antibodies in phase III clinical trials.
  • To highlight PCSK9 inhibitors as a novel hypolipidemic treatment option.

Main Methods:

  • Review of existing observational data and clinical trial results.
  • Analysis of the pharmacological action of PCSK9 inhibition.
  • Synthesis of safety and efficacy data from phase III studies of PCSK9 antibodies.

Main Results:

  • PCSK9 antibodies demonstrate a potent LDL-C lowering effect.
  • Phase III studies indicate favorable safety and efficacy profiles for PCSK9 inhibitors.
  • These agents represent a significant advancement in managing hyperlipidemia and reducing CVD risk.

Conclusions:

  • PCSK9 antibodies provide a novel therapeutic strategy for managing hyperlipidemia.
  • They offer an effective option for patients with statin-intolerant or statin-resistant hypercholesterolemia.
  • This class of drugs holds significant promise for further reducing residual CVD risk.