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Related Concept Videos

meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H01:13

meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H

6.8K
All meta-directing substituents are deactivating groups. These substituents withdraw electrons from the aromatic ring, making the ring less reactive toward electrophilic substitution. For example, the nitration of nitrobenzene is 100,000 times slower than that of benzene because of the deactivating effect of the nitro group. The first step in an electrophilic aromatic substitution is the addition of an electrophile to form a resonance-stabilized carbocation. The energy diagrams for...
6.8K
2° Amines to N-Nitrosamines: Reaction with NaNO201:20

2° Amines to N-Nitrosamines: Reaction with NaNO2

5.5K
Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
5.5K
SN2 Reaction: Kinetics02:14

SN2 Reaction: Kinetics

10.4K
Kinetic Studies and Significance
In a chemical reaction, a relationship exists between the concentration of reactants and the rate at which the reaction proceeds. The study to measure this relationship is known as the kinetics of a chemical reaction. Kinetic studies are used to deduce the rate law of a chemical reaction, which provides information about the species involved during the transition state of the rate-determining step. Thus, kinetic studies help to derive the mechanism of a...
10.4K
SN2 Reaction: Mechanism02:27

SN2 Reaction: Mechanism

17.6K
The kinetic studies of SN2 reactions suggest an essential feature of its mechanism: it is a single-step process without intermediates. Here, both the nucleophile and the substrate participate in the rate-determining step.
The presence of the more electronegative halogen in the substrate creates a polarized carbon-halide bond. The halide pulls the electron cloud generating an electrophilic center at the carbon atom. Thus, the carbon atom carries a partial positive charge while the halide has a...
17.6K
SN2 Reaction: Transition State02:26

SN2 Reaction: Transition State

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An SN2 reaction of an alkyl halide is a single-step process in which bond formation between the nucleophile and the substrate and bond breaking between the substrate and the halide occurs simultaneously through a transition state without forming an intermediate.
When the nucleophile approaches the electrophilic carbon with its lone pairs, the halide acts as a leaving group and moves away with the electron-pair bonded to the carbon. Dotted partial bonds represent the bonds being formed or broken...
12.1K
SN2 Reaction: Stereochemistry02:23

SN2 Reaction: Stereochemistry

11.9K
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not...
11.9K

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Examining BCL-2 Family Function with Large Unilamellar Vesicles
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Targeting BCL-2 in Hematologic Malignancies.

Nadia Khan1, Brad Kahl2

  • 1Fox Chase Cancer Center, Philadelphia, PA, USA. Nadia.Khan@fccc.edu.

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This summary is machine-generated.

Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor, targets cancer

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Resistance to apoptosis is a key feature of cancer.
  • The B-cell lymphoma 2 (BCL-2) protein family regulates apoptosis and is often upregulated in cancers, leading to chemotherapy resistance.
  • BCL-2 proteins are therefore attractive therapeutic targets for cancer treatment.

Purpose of the Study:

  • To describe Venetoclax, a small-molecule inhibitor targeting BCL-2 proteins.
  • To highlight Venetoclax's mechanism of action as a BCL-2 homology domain 3 (BH3) mimetic.
  • To summarize the clinical development and approved indications of Venetoclax.

Main Methods:

  • Venetoclax functions as a BCL-2 homology domain 3 (BH3) mimetic.
  • It is an orally administered small molecule.
  • Clinical trials assess its efficacy in various hematological malignancies.

Main Results:

  • Venetoclax is approved as a monotherapy for certain chronic lymphocytic leukemia (CLL) patients in the USA and EU.
  • The drug is in Phase III clinical development for multiple myeloma (MM).
  • Phase II or I/II trials are ongoing for acute myeloid leukemia and other B-cell malignancies, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, and mantle-cell lymphoma.

Conclusions:

  • Venetoclax is an effective apoptosis stimulant targeting BCL-2 proteins.
  • Its approved use in CLL and ongoing trials in other hematological cancers demonstrate its therapeutic potential.
  • Venetoclax represents a significant advancement in targeting BCL-2-driven cancers.