Pharmacology

Advancing your drug discovery process is our goal. Presude Lifesciences is committed to adding value to your journey in discovering transformational medicines in areas where it can make a meaningful difference for patients worldwide: oncology, immunology, autoimmunity and infectious diseases.

Our aim is to provide you with truly differentiated services in the areas shown below.


Target Validation

Presude Lifesciences adopts a multipronged approach to validate your target before you embark on you drug discovery process.

Pharmacological Validation

  • Validation using known inhibitors
  • Testing in in vivo disease models to clarify target MoA

Genetic Validation

  • Gene knock-in appropriate cell lines using shRNA, CRISP-R
  • Phenotype associated with knock-out and/or transgenic expression

Translational Studies

  • Ex vivo approaches such as patient derived explants (PDE) and patient derived xenograft (PDX) studies

Custom Assay Development

Presude’s custom assay development services provide recombinant proteins and genetically modified cell lines to suit your screening needs. We develop customized assays that are optimized using appropriate reference compounds. Our rapid turn around time is aimed to jumpstart your drug screening efforts along with round the clock consultation and assistance from the Presude team.

Assay Development & Optimization >> Assay Transfer / Bridging Studies

Design
  • Selection of assay format, pharmacological reagents, cell lines and relevant controls
Pre-study Validation
  • Optimization of assay variables, testing for screening conditions in laboratory
In-study Validation
  • Assay adaptation for screening
  • Support for early testing in lab, verification using controls
Cross-Validation
  • Implementation in discovery labs for routine screening

In Vitro Biochemical and Cellular Screening

Presude provides fully customized assays for enzymes, GPCRs, interleukins, cytokine and nuclear receptors. The assays are designed to understand the interaction of small molecule drugs with the target and provide information on target occupancy/engagement, nature of binding, kinetics of binding, species cross reactivity, isoform selectivity, etc.

Assay Formats

Absorbance
Florescence
Luminescence
Florescence Polarization

Flow Cytometry
HTRF
NanoBRET, TR-FRET
Alpha-ELISA

Equipment and Technology

Multimode Readers
Real-time PCR System
Microarray
SDS-PAGE

Flow cytometry
ELISA/Luminex
Engineered Cell Lines
Nanostring

Immune Functional Assays and MoA

Presude has developed multiple cell based assays using primary cells or cell lines to better understand your target MoA and its modulation by specific inhibitors. A representative set of assays is listed below:

Immune Cell Characterisation
  • T cell subsets: TH1/TH2/TH17: upregulation of activation markers, proliferation, cytokine release
  • B cells: upregulation of activation markers, proliferation, Ig release
  • Dendritic cells: Maturation of PBMC derived monocytes to pDC or mDC, antigen cross-presentation
  • Macrophages: Phagocytosis assay

Regulatory Cells
  • Tregs functional assays: inhibition of effector T cell proliferation and cytokine release
  • MDSCs functional assays: CD33+ or CD11b+ MDSC: Arginase activity, ROS production

Functional Assays for T cells
  • Immune cell stimulation and activation markers
  • Cytokine production
  • Proliferation, cytotoxicity, apoptosis

Ex vivo Assays
  • Pharmacodynamic assays and immune functional assays from in vivo studies
  • Target engagement assays

Translational
  • Patient derived explants and transcriptome signatures
  • PDX cell lines and in vitro co-culture assays

Cellular Assays

Oncology

  • Cytotoxicity assays
    • CCK8, LDH, Propidium Iodide and CFSE labelled cells, MTT, Alamar blue
  • Cell migration and apoptosis assay
  • Immunophenotyping of TILS in xenograft models
  • Complement-dependent cytotoxicity
  • Antibody-dependent cytotoxicity
  • Antibody-dependent phagocytosis

Inflammation/Autoimmunity

  • Cell surface markers by flow cytometry
  • B cell activation and Ig release assays
  • Ag-specific T-cell proliferation and cytokine release assay for CD4 and CD8 T cells, NK T cells, cytotoxic T cells
  • Assays for Tregs, MDSC
  • Dendritic cell maturation: pDC and mDCs and APC functional assays
  • Monocyte differentiation to macrophages and macrophage functional assays

Immuno-oncology

  • In vitro assays (small molecules, bispecifics, engineered Abs)
    • Binding studies: BIACORE, FACS
    • Immune cell mediated killing of cancer cells in co-culture assays (primary immune cells isolated from hPBMCS)
    • Activation markers on immune cells by FACS, qPCR, cytokine release (Multipex/Luminex)
    • ADCC, ADCP, MLR
    • Evaluation of biosimilars
  • Ex vivo studies
    • Immunophenotyping of TILS, activation markers, cytokine profile
    • Transcriptome analysis

The Presude PROTAC Toolkit

Acquired resistance to therapy has become the major problem facing current cancer treatment. Proteolysis targeting chimeras (PROTACs) have attracted a great deal of attention in the field of oncology for their sensitivity to drug-resistant targets. The PROTAC technology relies on degrading the target protein instead of inhibiting it. Presude has developed a PROTAC Toolkit to expedite your PROTAC drug discovery process by offering customized assays that establish your target MoA.

PROTACs Characterization Toolkit

Target binding / affinity
Florescence polarization, TR-FRET
Target
degradation
In cell-western / western blot
Ternary complex formation
ALphaLISA (cell free)
Target
engagement
NanoBRET (cell based)
Target
ubiquitination
NanoBRET ubiquitination assay

In Vivo studies

In Vivo Pharmacology Models

  • Autoimmunity
  • Inflammation
  • Oncology
  • Anti-infective

Managed at partner site