The dawn of hedgehog inhibitors: Vismodegib
نویسندگان
چکیده
منابع مشابه
Inhibitors of Hedgehog Acyltransferase Block Sonic Hedgehog Signaling
Inhibition of Sonic hedgehog (Shh) signaling is of great clinical interest. Here we exploit Hedgehog acyltransferase (Hhat)-mediated Shh palmitoylation, a modification critical for Shh signaling, as a new target for Shh pathway inhibition. A target-oriented high-throughput screen was used to identify small-molecule inhibitors of Hhat. In cells, these Hhat inhibitors specifically block Shh palmi...
متن کاملPharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent Hedgehog pathway activation.
PURPOSE Vismodegib (GDC-0449) is a potent and selective inhibitor of the Hedgehog (Hh) pathway that shows antitumor activity in preclinical models driven by mutational or ligand-dependent activation of the Hh pathway. We wished to characterize the pharmacokinetic-pharmacodynamic (PK/PD) relationship of vismodegib in both model systems to guide optimal dose and schedule for vismodegib in the cli...
متن کاملCombination of ponatinib with Hedgehog antagonist vismodegib for therapy-resistant BCR-ABL1-positive leukemia.
PURPOSE The Hedgehog signaling pathway is a key regulator of cell growth and differentiation during development. Whereas the Hedgehog pathway is inactive in most normal adult tissues, Hedgehog pathway reactivation has been implicated in the pathogenesis of several neoplasms including BCR-ABL1-positive leukemia. The clear link between the Hedgehog pathway and BCR-ABL1-positive leukemia led to an...
متن کاملComplete and sustained response of adult medulloblastoma to first-line sonic hedgehog inhibition with vismodegib.
Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults belong primarily to the SHH category. Vi...
متن کاملVismodegib, an antagonist of hedgehog signaling, directly alters taste molecular signaling in taste buds
Vismodegib, a highly selective inhibitor of hedgehog (Hh) pathway, is an approved treatment for basal-cell carcinoma. Patients on treatment with vismodegib often report profound alterations in taste sensation. The cellular mechanisms underlying the alterations have not been studied. Sonic Hh (Shh) signaling is required for cell growth and differentiation. In taste buds, Shh is exclusively expre...
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ژورنال
عنوان ژورنال: Journal of Pharmacology and Pharmacotherapeutics
سال: 2013
ISSN: 0976-500X
DOI: 10.4103/0976-500x.107628