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Related Concept Videos

Enzyme Inhibition01:30

Enzyme Inhibition

77.8K
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
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E2 Reaction: Kinetics and Mechanism02:45

E2 Reaction: Kinetics and Mechanism

9.8K
SN2 substitutions and E2 eliminations of alkyl halides proceed via a concerted pathway. While the nucleophile attacks the alpha carbon in SN2 reactions, it functions as a strong base and abstracts a beta hydrogen in the E2 mechanism. The rate-limiting transition state in E2 elimination reactions is characterized by partially broken carbon–hydrogen and carbon–halogen bonds and a partially formed pi bond between the alpha and beta carbons. The beta hydrogen and halide are eliminated...
9.8K
E1 Reaction: Stereochemistry and Regiochemistry02:43

E1 Reaction: Stereochemistry and Regiochemistry

9.2K
One of the critical aspects of the E1 reaction mechanism, as also observed in E2, is the regiochemistry, with multiple regioisomers obtained as products. In the example discussed, the presence of water as a weak base favors elimination over substitution to generate two alkenes. Given that alkenes’ stability increases with the number of alkyl groups across the double bond, typically, E1 reactions lead to the Zaitsev product, for this is more substituted and stable than the Hofmann product.
9.2K
Allosteric Regulation01:08

Allosteric Regulation

57.6K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
57.6K
E2 Reaction: Stereochemistry and Regiochemistry02:43

E2 Reaction: Stereochemistry and Regiochemistry

11.2K
Elimination reactions of alkyl halides can yield one or more alkenes depending on the specific regiochemical and stereochemical considerations. While the regiochemistry of the reaction governs the location of the double bond in the product, the stereochemical requirements often influence the geometry.
When a substrate with two different β hydrogens undergoes an E2 elimination, the presence of a strong base can yield two regioisomeric alkenes. The more-substituted alkene is the major...
11.2K
α-Alkylation of Ketones via Enolate Ions01:10

α-Alkylation of Ketones via Enolate Ions

3.0K
Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the...
3.0K

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Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
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EML4-ALK: Update on ALK Inhibitors.

Alessandra Bearz1, Elisa Bertoli1, Brigida Stanzione2

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International Journal of Molecular Sciences
|January 11, 2025
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This review covers advancements in treating ALK-positive non-small cell lung cancer using tyrosine kinase inhibitors. It discusses first-line treatment options and factors influencing inhibitor selection for better patient outcomes.

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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
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Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) is a distinct subtype.
  • Tyrosine kinase inhibitors (TKIs) have revolutionized treatment for advanced ALK-positive NSCLC.
  • Numerous ALK inhibitors are available for first-line and subsequent treatment lines.

Purpose of the Study:

  • To review the evolution of ALK inhibitor treatment in metastatic NSCLC.
  • To analyze survival outcomes associated with different ALK inhibitors in first- and second-line settings.
  • To present current first-line treatment strategies and decision-making factors.

Main Methods:

  • Literature review of clinical trials and real-world data on ALK inhibitors.
  • Analysis of survival data and efficacy outcomes for various ALK inhibitors.
  • Discussion of molecular profiling, resistance mechanisms, and patient comorbidities.

Main Results:

  • Significant progress in survival outcomes for ALK-positive NSCLC patients treated with TKIs.
  • Two primary first-line treatment approaches: sequential inhibition versus upfront potent inhibitor.
  • Importance of considering molecular characteristics and patient factors in treatment selection.

Conclusions:

  • Treatment decisions for ALK-positive NSCLC require a personalized approach.
  • Balancing efficacy, resistance profiles, and toxicity is crucial for optimal first-line therapy.
  • Ongoing research aims to further refine treatment strategies for this patient population.