Get ‘Kinome’ and mechanistic insights of your biological model

Measuring kinase activity allows insights in cellular signaling, pathway elucidation, target interaction and the ability to discover biomarkers.

Get ‘Kinome’ and mechanistic insights of your biological model

Measuring kinase activity allows insights in cellular signaling, pathway elucidation, target interaction and the ability to discover biomarkers.

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

Pathway elucidation

Dive deeper into relevant pathways in cancer, immune signaling, metabolic, central nervous system or cardiovascular diseases
Elucidate pathways in mutants, knockouts, or as a result of in vitro treatments
Deduce pathways altered in drug responses (like resistance)
Capitalize on a broad range of pathways using without depending on specific antibodies

Biomarker discovery

On-chip pharmacology capabilities lend a new approach to discovering therapy-predictive, disease specific and prognostic or pharmacodynamic biomarkers.

Biochemical characterization

Kinase enzymology, substrate identification for novel, mutated or post-translationally modified kinases.

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

Target discovery

Discover novel drug targets to guide drug development, where no prior target information is required.

Target interaction

Find the mechanism of action of small molecule or develop (surrogate) PD-markers.

“While quantitative measurements of transcripts and proteins are key to investigate the state of a biological system, they do not inform the “active” state of regulatory networks.” “Recent advancements of high-throughput protein kinase activity profiling platforms allow for a broad assessment of protein kinase networks in complex biological systems. In conjuncation with sophisticated computational modeling techniques, these profiling platforms provide datasets that inform the active state of regulatory systems in disease models and highlight potential drug targets.”

Learn more about this recently published review paper in ‘The current opinion in pharmacology’

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Technology

In order to study kinases in biological systems, we have developed a unique 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 from only a few thousand cells or small amounts (0.5-5 𝜇g protein) from animal, or human sources (tissue or cells) to determine the real-time activity of all kinases present in these lysates. In addition, clinical samples can be used since our technology only needs 10.000 cells (or 1 mm3 of biopsy material) as input, compared to 1×108 cells for mass spectrometry-based proteomic assays.

This is accomplished by actively incubating the lysates across 196 to 144 tyrosine (PTK) or serine/threonine kinase (STK) peptide substrates immobilized on the PamChip microarray platform. Our 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. The phosphosites on the PamChips are human-derived and there is significant overlap with other organisms including rodents. PamChip microarrays are processed on the fully automated PamStation.

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.

OUR TECHNOLOGY

“We were looking for an additional in-house technology that would support us in improving our analysis of pathway signaling. PamGene’s unique technology, measuring all kinases and their activity in a lysate, has proven to be the best fit for this. It provides a full mechanistic insight and it is possible to combine with additional data-sets. Our hypothesis analyses have been improved and the PamStation provides us with data sets that add enormous value to ongoing research projects and collaborations which ultimately can be published in well-known scientific journals.”

Dr. Astrid Weiß, post doc. at the Biomedical Research Center Seltersberg of the Justus-Liebig-University in Giessen, Germany and scientist at the German Center for Lung Research.

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Cases we’ve worked on

We have over 15 years of experience in the field of kinase science and contributed to over 100+ publications with top European, North American and Japanese Institutes.

To learn how our services contributed to different studies, request access to our case report.

Case report

Technology

OUR TECHNOLOGY

Products and services

We offer Contract Research Services tailored to your wishes, needs and research questions. It is also possible to obtain your own PamStation. The PamGene team will support you in making the PamStation an integral part of your research facility’s departments by providing in-house training and support.

Products and services

Scientific background

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

Sawada, T. et al.
Oncotarget 9, 34229–34239 (2018).

Publication

Intratumoral spatial heterogeneity of BTK kinomic activity dictates distinct therapeutic response within a single glioblastoma tumor.

Ibrahim AN, Yamashita D, Anderson JC, Abdelrashid M, Alwakeal A et. al.
J Neurosurg. Oct 18:1-12.(2019)

Publication

Analysis of Jak2 catalytic function by peptide microarrays: the role of the JH2 domain and V617F mutation.

Sanz A, Ungureanu D, Pekkala T, Ruijtenbeek R, Touw IP, Hilhorst R, Silvennoinen O.
PLoS One. (2011) Apr 18;6(4):e18522.

Publication

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