Related Experiment Video

Updated: Jul 17, 2026

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
11:23

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase

Sheldon Holder1, Marina Zemskova, Chao Zhang

  • 1Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, 11234 Anderson Street, Loma Linda, CA 92354, USA.

Molecular Cancer Therapeutics
|January 16, 2007
PubMed

Insights

Quercetagetin selectively inhibits pim-1 kinase, a cancer-driving enzyme. This cell-permeable compound effectively reduces prostate cancer cell growth, offering a potential tool for developing new PIM1-targeted therapies.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Pim-1 kinase is a known oncogene implicated in various cancers, including leukemia, lymphoma, and prostate cancer.
  • Targeting pim-1 kinase is a focus for drug development programs aimed at cancer treatment.
  • There is a need for selective, cell-permeable small-molecule inhibitors for studying pim-1 kinase function.

Purpose of the Study:

  • To identify and characterize a selective, cell-permeable small-molecule inhibitor of pim-1 kinase.
  • To evaluate the efficacy of the identified inhibitor in preclinical cancer models.
  • To provide a tool for basic and translational research on pim-1 kinase.

Main Methods:

  • Screening of a diversity library using an ELISA-based kinase assay to identify inhibitors.
  • Structural analysis of PIM1 in complex with identified inhibitors using X-ray crystallography.
  • In vitro and in cell-based assays to determine inhibitor potency, selectivity, and cellular effects.

Main Results:

  • Quercetagetin was identified as a moderately potent (IC50 = 0.34 μmol/L), ATP-competitive inhibitor of pim-1 kinase.
  • Crystal structures revealed diverse binding poses of quercetagetin and related flavonoids in PIM1.
  • Quercetagetin demonstrated high selectivity for PIM1 over PIM2 and other kinases, and inhibited PIM1 in prostate cancer cells (ED50 = 5.5 μmol/L).
  • Quercetagetin treatment led to significant growth inhibition of prostate cancer cells, correlating with PIM1 levels.

Conclusions:

  • Quercetagetin is a moderately potent, selective, and cell-permeable inhibitor of pim-1 kinase.
  • The findings support the use of quercetagetin for proof-of-concept studies in PIM1-related cancers.
  • This inhibitor may aid in the development of novel PIM1-targeted cancer therapeutics.

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

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...
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...