LDE225

An oral, selective inhibitor of Smoothened

• Smoothened (Smo) is a GPCR-like (G protein-coupled receptor) molecule that positively regulates Hedgehog (Hh) signal transduction, a signalling pathway that plays a critical role in the development and homeostasis of many organs and tissues.⁴⁵
• The Hh pathway is inactive in the absence of ligands as Smo is inhibited by the receptor Patched (Ptch). When Ptch is bound by one of the Hh family of ligands, such as Sonic Hedgehog (SHh), Desert Hedgehog (DHh), and Indian Hedgehog (IHh), activation occurs.⁴⁵
• Genetic activation of the Hh pathway at or upstream of Smo is linked to tumorigenesis of several cancers.⁴⁵
• LDE225 is a selective, orally bioavailable Smo antagonist from a novel structural class and has been shown to potentially inhibit Hh-and Smo-dependent proliferation in vivo.
• LDE225 is currently being investigated in a Phase I trial in patients with advanced solid tumors.

All compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.

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