PREDICTIVE TOXICITY

PREDICTIVE TOXICITY

Liver, heart, kidney and brain drug-induced toxicities currently account for more than 70% of drug attrition and drug withdrawal. Porsolt together with Fluofarma has developed a range of organ-specific cell-based assays to better predict the toxicity potential of drug candidates.

CELL-BASED ASSAYS

Based on highly predictive cellular models, i.e. primary cell cultures, Fluofarma our affiliate,  performs functional toxicity assays and offers to investigate the signaling pathways involved in detoxification and oxidative stress induced by the drug compound.

GENERAL TOXICITY

IN VIVO
Acute toxicity Rat - Mouse - Dog - Mini-pig TOX 11

Preliminary chronic toxicity

Rat - Mouse TOX 12

HEPATOTOXICITY

IN VITRO
Cholestasis/Bile canaliculi network Primary hepatocytes (H,R,M) sandwich configuration PF 3.16
Lipid, intracellular accumulation: triglycerides Primary hepatocytes (H,R,M)  HepG2 PF 3.30
NAD(P)H/FAD Primary hepatocytes (H,R,M)  HepG2 PF 3.31
Mitochondrial membrane potential Primary hepatocytes (H,R,M)  HepG2 PF 3.3
Cytolysis Primary hepatocytes (H,R,M)  HepG2 PF 3.4
MRP2 expression measurement Primary hepatocytes -
 sandwich configuration-
hepatic tissue
PF 3.5

NEPHROTOXICITY

IN VITRO
Lysosomal activity

Primary human renal proximal tubule epithelial cells

Human renal proximal tubule epithelial cell line (HK-2)

PF 3.7
Mitochondrial membrane potential PF 3.3
Cytolis PF 3.4

NEUROTOXICITY

IN VITRO
Neurite outgrowth

Primary neurons (R,M)

iPSC derived neurons,
cell lines



PF 3.6
Cytolysis PF 3.4
Caspase 3/7 activation PF 3.2

GENOTOXICITY

IN VITRO
Histone H2AX phosphorylation Multiple cellular models PF 5.1
IN VIVO
Mammalian erythrocyte
micronucleus assay
Rat TOX 17

CARDIOTOXICITY

IN VITRO
Drug Induced Vascular Injury
(Endothelial Cell Activation markers)

HUVECs

PF 11.1
COMPREHENSIVE IN VITRO PROARRHYTHMIA ASSAY (CIPA):
Proarrhythmic risk assessment
(MEA & Calcium transient assay)

human-induced pluripotentstem cell-derived cardiomyocytes (hiPSC-CMs) CV 5.14
Electrophysiology measurement   (conventional manual patch-clamp) Cardiac ion channels CV 5.6 to CV 5.9

OUR GLOBAL EXPERTISE IN PREDICTIVE TOXICOLOGY