The dawn of hedgehog inhibitors: Vismodegib.

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Sandhiya S, Melvin G, Kumar SS, Dkhar SA

The dawn of hedgehog inhibitors: Vismodegib.

J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628.

PubMed ID

23662017 [ View in PubMed

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Abstract

Cancer, one of the leading causes of death worldwide is estimated to increase to approximately 13.1 million by 2030. This has amplified the research in oncology towards the exploration of novel targets. Recently there has been lots of interest regarding the hedgehog (Hh) pathway, which plays a significant role in the development of organs and tissues during embryonic and postnatal periods. In a normal person, the Hh signaling pathway is under inhibition and gets activated upon the binding of Hh ligand to a transmembrane receptor called Patched (PTCH1) thus allowing the transmembrane protein, smoothened (SMO) to transfer signals through various proteins. One of the newer drugs namely vismodegib involves the inhibition of Hh pathway and has shown promising results in the treatment of advanced basal-cell carcinoma as well as medulloblastoma. It has been granted approval by US Food and Drug Administration's (US FDA) priority review program on January 30, 2012 for the treatment of advanced basal-cell carcinoma. The drug is also being evaluated in malignancies like medulloblastoma, pancreatic cancer, multiple myeloma, chondrosarcoma and prostate cancer. Moreover various Hh inhibitors namely LDE 225, saridegib, BMS 833923, LEQ 506, PF- 04449913 and TAK-441 are also undergoing phase I and II trials for different neoplasms. Hence this review will describe briefly the Hh pathway and the novel drug vismodegib.

DrugBank Data that Cites this Article

Drugs

Vismodegib

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Vismodegib	Smoothened homolog	Protein	Humans	Yes	Antagonist Inhibitor	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Vismodegib	Cytochrome P450 2C9	Protein	Humans	No	Substrate Inhibitor	Details
Vismodegib	Cytochrome P450 3A4	Protein	Humans	No	Substrate	Details

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Vismodegib	P-glycoprotein 1	Protein	Humans	Unknown	Substrate	Details