Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Transplantation

Graft-versus-host disease (GvHD)

Smoothened (SMO)

Mouse and patient studies suggest inhibiting SMO to reduce hedgehog pathway signaling could help prevent or treat sclerodermatous GvHD. In patients with sclerodermatous GvHD, hedgehog pathway signaling was greater than that in healthy controls. In a mouse model of sclerodermatous GvHD, a SMO inhibitor prevented disease onset and blocked progression of established disease, whereas an inactive control treatment did not. Next steps include testing the effects of SMO inhibition in preclinical models of other types of GvHD.
Erivedge vismodegib, a small molecule SMO inhibitor from Roche, its Genentech Inc. unit, Chugai Pharmaceutical Co. Ltd. and Curis Inc., is marketed to treat basal cell carcinoma (BCC).
LDE225, a SMO inhibitor from Novartis AG, is in Phase III testing to treat BCC.
At least four other companies have SMO inhibitors in Phase I testing or earlier to treat various cancers.

SciBX 5(37); doi:10.1038/scibx.2012.987
Published online Sept. 20, 2012

Patent application filed; licensing status unavailable

Zerr, P. et al. Blood;
published online Aug. 22, 2012;
doi:10.1182/blood-2012-01-403428
Contact: Jörg H.W. Distler,
University of Erlangen-Nuremberg, Nuremberg, Germany
e-mail:
joerg.distler@uk-erlangen.de