Brain Tumours

LDE225: Preclinical Summary

3000 Tumour volume (mm 3 ) 1000 1500 2000 2500 3000

Ptch +/-, p53 -/- MB model

LDE225

Vehicle

Tumour volume (mm 3 ) mean ± SEM

5mg/kg

Gli-1 mRNA (human) Luciferase (mouse)

8 10 12 14 16 18 20 22 0 500

10 mg/kg 20 mg/kg

Gli-1 promoter

Days post-implantation

Assay

Cell line

IC 50

(nM)

Shh-induced Gli-1 mRNA

Human HEPM

13

 LDE225 is a novel oral inhibitor of Smo that potently inhibits Smo- dependent proliferation in vivo in preclinical studies

Shh-induced Gli-1 Luciferase

Mouse TM3

7

Gli, glioma-associated oncogene homolog zinc finger protein; Shh, Sonic Hedgehog

LD E22