Stattic: a small-molecule inhibitor of STAT3 activation and dimerization

Related Experiment Video

Updated: Jul 18, 2026

Protein Purification-free Method of Binding Affinity Determination by Microscale Thermophoresis
10:22

Protein Purification-free Method of Binding Affinity Determination by Microscale Thermophoresis

Published on: August 15, 2013

Jochen Schust1, Bianca Sperl, Angela Hollis

  • 1Department of Molecular Biology, Independent Research Group, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.

Chemistry & Biology
|November 23, 2006
PubMed

Insights

Stattic, a novel small molecule, selectively inhibits Signal transducer and activator of transcription 3 (STAT3) function by targeting its SH2 domain. This inhibition reduces STAT3 activation and promotes apoptosis in STAT3-dependent cancer cells.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Drug Discovery

Background:

  • Signal transducers and activators of transcription (STATs) are key transcription factors.
  • STAT3 is constitutively activated in many cancers, driving tumor growth.
  • Targeting STAT3 activation is a promising cancer therapy strategy.

Purpose of the Study:

  • To identify and characterize small molecules that inhibit STAT3 function.
  • To evaluate the efficacy of Stattic in preclinical cancer models.

Main Methods:

  • Chemical library screening for STAT3 inhibitors.
  • In vitro assays to assess STAT3 SH2 domain inhibition.
  • Cell-based assays measuring STAT3 activation, dimerization, and nuclear translocation.
  • Assessment of apoptosis rates in cancer cell lines.

Main Results:

  • Stattic, a nonpeptidic small molecule, was identified.
  • Stattic selectively inhibits STAT3 SH2 domain function in vitro.
  • Stattic blocks STAT3 activation, dimerization, and nuclear translocation.
  • Stattic increases apoptosis in STAT3-dependent breast cancer cell lines.

Conclusions:

  • Stattic is a potent and selective inhibitor of STAT3.
  • Stattic demonstrates potential as a therapeutic agent for STAT3-driven cancers.
  • Stattic serves as a valuable tool for studying STAT3 function in cancer models.

More Related Videos

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

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...
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...
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...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...