IPS's IDDP™, an unique drug discovery system, is a standard platform of drug discovery which can rapidly and economically find out lead materials and druggable candidates ranging from target analysis to lead optimization. It includes technologies such as "in silico structure-based drug design", "Protein chip-based screening & profiling" and "Cell-based assay"
In silico virtual screening of an inhibitor was carried out from the pytochemical library on the basis of structure of OPN binding site of integrin αvβ3. The inhibitors were further screened by protein chip-based screening method based on competitive inhibition assay of OPN-Integrin interaction in a dose-dependent manner.The biological function of the active lead compounds were analyzed by cell-based and in vivo assay including osteoclast differentiation and bone resorption.
Background and unmet needs
In osteoporosis drug market, the majority of the current treatment of osteoporosis are supplements and preventive agent. In addition, the effect is not enough for treatment. Moreover, the side effects were reported. Therefore, the new target of the drug is needed.
Discovery and Achievements
Molecular target: Osteopontin (OPN), integrin αvβ3
Mechanism of action:
IPS-02001 is a specific inhibitor of protein-protein interaction (PPI) between osteopontin and integrin αvβ3.
Indication(s) proposed for the compound(s):
IPS-02001 prevents and treats Osteoporosis
Potency of the compound in relevant in vitro assays:
IPS-02001 specifically inhibit OPN in substrate of Integrin αvβ3.
IPS-02001's IC50 is higher than Alendronate. In 0.6μM (low concentration), Alendronate is not efficacy, but
IPS-02001 inhibit RANKL.
Potency of the compound when given to animals, route of administration
IPS-02001 has inhibitory activity of bone-resorption in the mouse model and has effect of treatment on the OVX mouse model as shown in following figures.
Toxicology and safety report summary
Pre-clinical test - Toxicity test of IPS-02001 is as follows;
· Ames Test : Negative
· Chromosomal Aberration Assay : Negative
· Micronucleus Assay : Negative
· Acute oral toxicity : 2000mg/kg (MLD) (RAT)
PK test of IPS-02001 is as follows;
· Transcytosis Test : 70% ~ 80%, · Protein Binding : non-specific biding(NSB) - Negative
· Metabolic stability : Excellent stability
· Cyp450 : Inhibition of CYP metabolic enzymes is low
· Fomulation Analysis : Concentration of 1mg/ml and 200mg/ml is stable.