Purpose

Lead characterization and optimization is a crucial stage in the drug discovery process where molecules identified as promising candidates to treat different pathological conditions are characterized and optimized in terms of their potency, selectivity, pharmacokinetic properties and safety profile.

Therapeutic areas:

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Antibodies

Target identity/validation (High throughput free immobilization immunoassays)
Antibody engineering (affinity maturation; single-domain antibodies; humanization, solubility and half-life optimization; stability profile)
Antibody screening using in vitro phage display
Antibody library construction in several formats (scFv, Fab, sdAbs) and types (imune, naϊve or synthetic)
Single B cell screening
Antibody sequence analysis
Functional assays: binding assays; antibody dependent cellular cytotoxicity or phagocytosis assays; agonistic/blocking assays; cell reporter assays

ADME-Tox studies

in vitro ADME-Tox assays

The in vitro assays provide valuable data for deciphering the mechanisms and drug-related determinants underlying the drug candidates’ journey in the body and predicting the in vivo pharmacokinetic (PK) and pharmacodynamics (PD) profiles.

in vivo pharmacokinetic assays (in rodents)

In in vivo PK studies, compounds are administered to rodents and samples collected over a pre-defined time period. The dosing regimen and sampling are designed according to the project needs and prior information available on the study compounds.

Services

Single or repeated dosing (i.p., i.v., p.o., s.c., i.m.)
Studies with small molecules, peptides and proteins
Plasma sampling, tissue and CSF collection
Bioanalysis by LC/MS/MS or UPLC/High-resolution-MS analysis

in vitro assays

Caco-2 Permeability
BBB permeability (rodents, humans, pigs, dogs)
Efflux Transporters (substrate and inhibition assays): A family of ATP binding cassette (ABC) transporters is an important group of membrane transporters involved in drug absorption, distribution and elimination. Regulatory authorities (EMA, FDA) recommend investigating the potential roles of ABC superfamily members ABCB1 (MDR1, P-glycoprotein), and ABCG2 (BCRP) for transporter-mediated drug-drug interactions (DDI), by evaluating whether the new drug candidate is a substrate (potential DDI victim) or an inhibitor (potential DDI perpetrator) towards drug transporters. Additionally, evaluation of inhibition towards bile salt export pump (BSEP, ABCB11) is recommended due to safety concerns associated with inhibition of this transporter
Uptake Transporters (substrate and inhibition assays): A family of solute carriers (SLC) is an important group of membrane transporters involved in drug absorption, distribution and elimination. Regulatory authorities (EMA, FDA) recommend investigating the potential roles of SLC superfamily members OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1 and MATE2 for transporter-mediated drug-drug interactions (DDI), by evaluating whether the new drug candidate is a substrate (potential DDI victim) or an inhibitor (potential DDI perpetrator) towards drug transporters. In addition, EMA suggests also considering investigation of OCT1, whenever in vitro and in vivo findings suggest its involvement in DDI to be anticipated

Lead Characterization and Optimization

Purpose

Therapeutic areas:

in vitro ADME-Tox assays

in vivo pharmacokinetic assays (in rodents)

Services

Services

Contacts