MedKoo product information:

 Erismodegib

Description of Erismodegib: Erismodegib (LDE225, NVP-LDE225) is an orally bioavailable small-molecule Smoothened (Smo) antagonist with potential antineoplastic activity. Erismodegib selectively binds to the Hedgehog (Hh)-ligand cell surface receptor Smo, which may result in the suppression of the Hh signaling pathway and, so, the inhibition of tumor cells in which this pathway is abnormally activated. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair. Inappropriate activation of Hh pathway signaling and uncontrolled cellular proliferation, as is observed in a variety of cancers, may be associated with mutations in the Hh-ligand cell surface receptor Smo. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:    Novartis Pharmaceuticals.

LDE225(NVP-LDE225) is a novel and specific, orally bioavailable Smo inhibitor with an IC50 of 11 nM. It has been shown to potentially inhibit Hh-and Smo-dependent proliferation in vivo. It also induced the regression of preformed basaloid lesions with an IC50 of <150 nmol/l and almost complete regression at 1.5 μmol/l. Topical application of a 1% LDE225(NVP-LDE225) solution to depilated skin of C57/BL6 mice completely inhibited hair growth during anagen phase as well as the expression of the Hh-pathway target genes (Gli1, Gli2, Sox9, and N-Myc) and partial inhibition was obtained when applying a 0.3% solution.

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8. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist By Pan, Shifeng; Wu, Xu; Jiang, Jiqing; Gao, Wenqi; Wan, Yongqin; Cheng, Dai; Han, Dong; Liu, Jun; Englund, Nathan P.; Wang, Yan; et al From ACS Medicinal Chemistry Letters (2010), 1(3), 130-134.

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10. Substituted biphenyl amide compounds and compositions as hedgehog pathway modulators By Gao, Wenqi; Jiang, Jiqing; Wan, Yongqin; Cheng, Dai; Han, Dong; Wu, Xu; Pan, Shifeng From PCT Int. Appl. (2007), WO 2007131201 A2 20071115.