PLATFORM FOR ACCELERATING THE DISCOVERY AND OPTIMIZATION OF NEW BIOACTIVE MOLECULES (ACUTE LEUKEMIA)

Drug design

ALL
MPAL
AML

Targeted therapy

Basic research (TRL 1-3)

Set of skills and technologies to accelerate the identification and optimization of small chemical molecules for therapeutic purposes.

Our objectives are to identify, understand, validate and target signaling pathways involving key targets in tumor development (enzymes, protein/protein interaction surfaces …), with the specific aim of facilitating the transfer of identified therapeutic / pharmacological targets to preclinical and clinical development programs in oncology. The aim is to shorten the time "from discovery to patent filing".

Description

Scope of research activities

Studies for the identification, validation and optimization of new drug candidates:

Miniaturized and automated experimental screening in vitro or in cellulo
Biophysical characterization and orthogonal validation
Optimization of drug candidates (hit-to-lead) using a semi-automated (Chemo)DOTS approach

Conducting studies

Steps :

Study design
Define means/resources and propose schedule (steps, GO/NO-GO, cost estimate)
Study organization, implementation and conduct
Data analysis and delivery of a study report with recommendations

Research infrastructure

Experimental and analysis platforms:

ACCESS integrated robotic platform (Beckman) with in-line Echo 650 acoustic transfer system (2.5nl drop), centrifuge, plate sealer, multimodal dispenser (Certus gyger) and microplate reader (Pherastar FS BMG Labtech)
384-well RT-PCR for TSA (CFX384 Biorad)
FPLC (Akta Pure Cytivia)
Microcalorimeter ITC200 (Malvern)
Incubators (cell culture & crystallography)
Database and calculation servers

Technologies :

Fluorescence
Luminescence
Absorbance
TR-FRET (HTRF®)
Protein thermostability (Thermal Shift Assay)
Isothermal calorimetric titration
Cytotoxicity (adherent and non-adherent cells)
Chemoinformatics (ChemoDOTS, CovaDOTS, Chemaxon, SeeSar, MOE)

Staff :

1 scientific manager and 1 operational engineer manager
1 researcher and 2 engineers - cell screening and HTS
1 researcher and 1 assistant engineer - molecular modeling & chemoinformatics

Quality assurance

IBiSA certification
Aix Marseille-Université Technology Platforms certification

Specifications

The studies

Target identification and characterization:

Expression in various prokaryotic systems
Biochemical production, purification and characterization

Experimental screening:

Development of miniaturized, automated assays in 384- or 1536-well plates (enzymatic assays, protein-protein interaction, cytotoxicity)
High-throughput screening on purified proteins or different cell types (adherent or suspension cell lines, primary cells). Use of acoustic Echo technology to transfer liquid nanodroplets to prepare screening plates.
Validation of 'touch molecules' in combination or dose-response.
Provision of commercial or in-house chemical libraries

Optimization:

Crystallization & co-crystallization. Resolution and analysis of the crystallographic structure of the "target/ligand" complex (if no 3D structure of the complex, modeling service available)
Integrated 'DOTS' approach: Chemoinformatics (ChemoDOTS), virtual screening
Search for adjacent 'pockets
Proposal of new molecules based on starting molecule - Study plan
List of new molecules to be prioritized for synthesis - Validation request
Custom synthesis / medicinal chemistry (possible service)

Examples of partnerships

Optimization of compounds for an epigenetic target - Based on a chemical starting structure (hit), proposal of optimizations by cycle (fragment-based drug design) to accelerate hit-to-lead.

Partner: EISAI

Custom synthesis of chemical compounds - Custom synthesis of compounds for a feasibility study.

Partner: CISBIO

Terms

OPALE entity

CRCM / IPC (UMR-1068)

Contact

Other offers

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