Discover, optimize and analyze your therapeutic kinase inhibitor candidates


Accelerate your kinase inhibitor R&D activities through our comprehensive kinase technology. Get insights into the drug’s mechanism of actions.

Discover, optimize and analyze your therapeutic kinase inhibitor candidates


Accelerate your kinase inhibitor R&D activities through our comprehensive kinase technology. Get insights into the drug’s mechanism of actions.

Kinases are the most intensively studied protein targets and are the basis of numerous types of therapies. However, the traditional approaches study the abundance of proteins rather than their activity. This results in a knowledge gap on how cell signaling really works and a partial understanding of your drug.

Building on 15 years of experience, PamGene has developed a unique technology making real-time measurement and understanding of kinase activity possible. Our functional phosphoproteomic assays bring on a new dimension and additional information about how cell signaling works in various disease areas.

Applications

 

We offer Contract Research Services tailored to your needs and research questions.

Kinase Inhibitor Discovery

Broad interrogation of the full range of kinases (~350) and screen for a match between your identified compound and a kinase resulting in a set of lead kinase inhibitors.

Compound-based Patient Stratification

Improvement and specification of your clinical trials through dividing your potential patient group into kinase related subgroups.

Diseases Model Characterization

Comparative analysis of your diseases model (in vitro or in vivo and human or rodent) with respect to healthy or wild type counterpart to gain disease specific kinome or signal transduction related information

Kinase Inhibitor Optimization

  • Selectivity and effectivity of your kinase inhibitor lead in relation to your target across a wide range of conditions and concentrations
  • Differentiation of primary and secondary effects of a kinase inhibitor
  • Quantification of the inhibitory effect on the activity of fully decorated kinases
  • Compound toxicity effects
  • Compound repositioning

Pathway elucidation

  • Elucidating signaling pathways altered in mutants, knockouts, or as a result of in vitro treatments
  • Deducing pathways altered in disease and acquired or innate resistance to drugs
  • Linking your research question to relevant cancer, immune signaling, cardiovascular diseases, and central nervous system disorders

Technology

 

In order to study kinases in biological systems, we have developed an innovative method to understand kinase activity in diverse disease areas and states. Our sensitive platform uses lysates obtained without the need for complex sample preparation steps.

Lysates are actively incubated across 196 to 144 tyrosine (PTK) or serine/threonine kinase (STK) peptide substrates immobilized on the PamChip® microarray platform. These 3D microarrays are spotted with peptides (i.e. phosphosites) that represent kinase targets. Kinases present in the lysates will phosphorylate the peptide substrates which are detected using fluorescently labelled antibodies.

Based on current online knowledge, we compiled a comprehensive, integrated database (DB) of potential kinases that are linked to the peptides on the PamChips. This corresponds to ~350 unique kinases in literature, covering the majority of the kinome.

Technology

 

In order to study kinases in biological systems, we have developed an innovative method to understand kinase activity in diverse disease areas and states. Our sensitive platform uses lysates obtained without the need for complex sample preparation steps.

Lysates are actively incubated across 196 to 144 tyrosine (PTK) or serine/threonine kinase (STK) peptide substrates immobilized on the PamChip® microarray platform. These 3D microarrays are spotted with peptides (i.e. phosphosites) that represent kinase targets. Kinases present in the lysates will phosphorylate the peptide substrates which are detected using fluorescently labelled antibodies.

Based on current online knowledge, we compiled a comprehensive, integrated database (DB) of potential kinases that are linked to the peptides on the PamChips. This corresponds to ~350 unique kinases in literature, covering the majority of the kinome.

Scientific background

The ALK inhibitor AZD3463 effectively inhibits growth of sorafenib-resistant acute myeloid leukemia.

 

Moharram SA, Shah K, Khanum F, Rönnstrand L, Kazi JU. (2019)
Blood Cancer J. Jan 15;9(2):5.

Publication

Multiparametric Assessment of the Effects of Tyrosine Kinase Inhibitors (TKIs) on the (Electro)physiology of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Cardiomyocytes.

de Korte T, Nacken P, Pijnenburg D, Ruijtenbeek R, Stevenhagen F, Wilbers R, den Hartogh S, Groten J, Braam S and Vlaming M
Journal of Pharmacological and Toxicological Methods. 88. 236-237. 10.1016. (2017)

Publication

Inactive immune pathways in triple negative breast cancers that showed resistance to neoadjuvant chemotherapy as inferred from kinase activity profiles.

Sawada T, Hilhorst R, Rangarajan S, Yoshida M, Tanabe Y, Tamura K, Kinoshita T, Shimoyama T, van Beuningen R, Ruijtenbeek R, Tsuda H, Koizumi F
Oncotarget. Sep 28;9(76):34229-34239. (2018)

Publication