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Related Concept Videos

Subviral Agents01:29

Subviral Agents

Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
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Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
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Post-approval, manufacturers may modify an approved new or generic drug product. Such modifications can encompass alterations in the Active Pharmaceutical Ingredient (API), manufacturing process, formulation, batch size, manufacturing site, and container closure system (FDA Guidance for Industry, April 2004). Often, a drug product may undergo multiple changes.These modifications require careful evaluation to determine their potential impact on the drug product's identity, strength, quality,...
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Targeted Cancer Therapies

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A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
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Published on: December 7, 2014

An update on dual Src/Abl inhibitors.

Francesca Musumeci1, Silvia Schenone, Chiara Brullo

  • 1Dipartimento di Scienze Farmaceutiche, University of Genoa, Viale Benedetto XV 3, I-16132 Genova, Italy.

Future Medicinal Chemistry
|April 26, 2012
PubMed
Summary

Dual tyrosine kinase inhibitors targeting c-Src and Bcr-Abl show promise for treating cancers like chronic myeloid leukemia. These multi-targeted compounds may overcome drug resistance, offering new therapeutic strategies.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cytoplasmic tyrosine kinases (TKs) c-Src and Bcr-Abl are implicated in various malignancies.
  • Bcr-Abl is the causative agent of chronic myeloid leukemia (CML), with c-Src also playing a role.
  • Elevated c-Src activity is observed in several solid tumors.

Purpose of the Study:

  • To review recent advancements in dual inhibitors targeting both c-Src and Bcr-Abl.
  • To highlight compounds in clinical trials and emerging in scientific literature.
  • To discuss the potential of multi-targeted TKIs over selective inhibitors.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of compounds targeting both Src and Abl tyrosine kinases.
  • Focus on dual inhibitors with reported clinical trial data.

Main Results:

  • Several dual Src/Abl inhibitors have demonstrated efficacy.
  • These compounds are valuable in overcoming resistance to TKIs in advanced CML.
  • Emerging research supports the effectiveness of multi-targeted inhibitors.

Conclusions:

  • Dual TKIs represent a promising therapeutic avenue for hematologic and solid tumors.
  • The development of multi-targeted inhibitors is driven by positive clinical outcomes and theoretical advantages.
  • This review provides an update on key dual inhibitors in development and clinical trials.