Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors PTCH and/or SMO and suppressing Hedgehog signaling. The Hedgehog signaling pathway plays an important role in tissue growth and repair; aberrant constitutive activation of Hedgehog pathway signaling and uncontrolled cellular proliferation may be associated with mutations in the Hedgehog-ligand cell surface receptors PTCH and SMO. It inhibits the growth of primary pancreatic xenografts without non-specifically inhibiting pancreatic cell proliferation in vitro and has recently entered the clinic. It also inhibits ABCG2, Pgp, and MRP1-important ABC transporters associated with MDR. The IC50 values of GDC-0449 (Vismodegib) for inhibition of ABCG2 and Pgp were about1.4 and 3.0 μM, respectively. It has been used to treat medulloblastoma in animal models.
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