Related Experiment Video

Updated: May 13, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

A combination strategy to inhibit Pim-1: synergism between noncompetitive and ATP-competitive inhibitors

Mattia Mori1, Cristina Tintori, Robert Selwyne Arul Christopher

  • 1Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy.

Chemmedchem
|February 26, 2013
PubMed

Insights

Researchers identified new Pim-1 kinase inhibitors, including novel non-competitive 2-aminothiazole derivatives. These compounds show synergistic effects with other inhibitors and paclitaxel, offering potential new cancer treatment strategies.

Area of Science:

  • Biochemistry
  • Oncology
  • Medicinal Chemistry

Background:

  • Pim-1 kinase is a key regulator in various cancers, including leukemia and solid tumors.
  • Pim-1 is a validated drug target for cancer therapy.

Purpose of the Study:

  • To discover novel potent Pim-1 inhibitors.
  • To explore new mechanisms of Pim-1 inhibition.

Main Methods:

  • Structure-activity relationship (SAR) studies of an indolyl-pyrrolone scaffold.
  • Virtual screening to identify new inhibitors.
  • Enzymatic and cell proliferation assays.

Main Results:

  • Identified novel ATP-competitive inhibitors.
  • Discovered 2-aminothiazole derivatives with a novel non-ATP-competitive mechanism.
  • Observed synergistic inhibition of Pim-1 activity and cancer cell proliferation with combined inhibitor types.
  • Demonstrated synergism with paclitaxel in prostate cancer cells.

Conclusions:

  • Pim-1 remains a promising cancer target.
  • Novel non-ATP-competitive inhibitors offer new therapeutic avenues.
  • Combined inhibition strategies show potential for overcoming resistance and enhancing efficacy.

More Related Videos

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

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

Published on: January 22, 2019

Related Concept Videos

Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Enzyme Inhibition01:30

Enzyme Inhibition

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.
Indirect-Acting Cholinergic Agonists: Mechanism of Action01:18

Indirect-Acting Cholinergic Agonists: Mechanism of Action

Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...