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Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...

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Related Experiment Video

Updated: Jun 16, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

NSC114792, a novel small molecule identified through structure-based computational database screening, selectively

Byung-Hak Kim1, Jun-Goo Jee, Chang-Hong Yin

  • 1Department of Pediatrics, Division of Hematology/Oncology, New York Medical College, Valhalla, New York 10595, USA.

Molecular Cancer
|February 13, 2010
PubMed
Summary

We identified NSC114792, a novel small molecule, that selectively inhibits Janus Kinase 3 (JAK3) activity. This compound shows therapeutic potential for diseases driven by aberrant JAK3 signaling, including certain cancers.

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Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
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Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

Related Experiment Videos

Last Updated: Jun 16, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
10:20

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Janus Kinase 3 (JAK3) is crucial for T-cell development and immune homeostasis.
  • Aberrant JAK3 signaling and mutations are implicated in hematopoietic malignancies and tumorigenesis.
  • JAK3 represents a promising therapeutic target for various human diseases.

Purpose of the Study:

  • To identify novel small molecule inhibitors of JAK3.
  • To evaluate the therapeutic potential of identified inhibitors in diseases driven by aberrant JAK3 activity.

Main Methods:

  • Structure-based virtual screening of the NCI diversity set against the JAK3 kinase domain.
  • In vitro biochemical assays to assess catalytic activity inhibition.
  • Cell-based assays to evaluate signaling pathway modulation and anti-cancer effects.

Main Results:

  • NSC114792 was identified as a lead compound that selectively inhibits JAK3 catalytic activity in vitro.
  • NSC114792 blocked IL-2-dependent JAK3/STAT5 activation but not IL-3-dependent JAK2/STAT5 activation.
  • NSC114792 selectively inhibited persistently-activated JAK3 in cancer cell lines and decreased cell viability by inducing apoptosis in relevant cancer cells.

Conclusions:

  • NSC114792 is a potent and selective JAK3 inhibitor.
  • This compound serves as a valuable starting point for developing novel therapeutics targeting JAK3.
  • Targeting aberrant JAK3 activity with small molecule inhibitors holds significant therapeutic potential for various diseases.