Mutant smoothened and methods of using the same
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United States of America Patent
Stats
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Jun 25, 2019
Grant Date -
Feb 15, 2018
app pub date -
Feb 4, 2016
filing date -
Feb 4, 2015
priority date (Note) -
In Force
status (Latency Note)
Importance
Abstract
The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, mutations in the serpentine receptor, Smoothened (SMO) are described, which result in resistance to a Hedgehog (Hh) pathway inhibitor, such as in medulloblastoma. Amino acid substitutions in conserved residues of SMO maintain Hh signaling, but result in the inability of the Hh pathway inhibitor, GDC-0449, to bind SMO and suppress the pathway. In some embodiments, the disclosure provides for novel mutant SMO proteins and nucleic acids and for screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.
First Claim
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International Classification(s)
- C07H:SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTI....
- A61K:PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOS....
- C12Q:MEASURING OR TESTING PROCESSES INVOLVING ENZYMES O....
- C12N:MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF
- G01N:INVESTIGATING OR ANALYSING MATERIALS BY DETERMININ....
- C07K:PEPTIDES
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