lecture 3 kinases Flashcards
what are kinase’s role?
catalyze transfer of phosphate groups
cell signaling is driven by transfer of phosphates
ATP is major source of phosphate
tyrosine, serine, threonine are used
what is the role of phosphatases?
balance activity of kinases by removing phosphates
what are the types of kinase inhibitors?
Type 1: bind to active conformation
Type 2: bind and stabilize the inactive conformation of kinase
Type 3: occupy an allosteric pocket outside the ATP-binding pocket
which drugs are EGFR targeted kinase inhibitors?
getfitinib
erlotinib
afatinib
osimertinib
what is gefiitinib?
EGFR targeted kinase inhibitor
approved NSCLC exon 19/20 mutations
T790M causes resistance to getfitinib
what is erlotinib?
reversible inhibitor EGFR
competitive inhibition by binding to ATP site
approved metastatic NSCLC exon 19/20 mutations
what is afatinib?
covalent inhibitor of all ErbB receptors
approved for EGFR mutant NSCLC w/ EGFR mutations
what is osimertinib?
covalent inhibitor for EGFR
approved for T790M
what are the HER2 inhibitors?
lapatinib
tucantinib
what is lapatinib?
irreversibly blocks HER2 and EGFR
selective for HER2+ breast cancer, approved (in combo with capecitabine) for metastatic breast cancer
reversible decrease in cardiac function –> watch for sx CHF
what is tucatinib?
selective treatment for HER2+ breast cancer
approved second line (combo with trastuzumab and capecitabine) for metastatic breast cancer
reduced sides compared to laptinib possibly bc of increased specificity to HER2
what is FLT mutation cause?
FLT3 is responsible for hemapoeitic cell survival and proliferation
mutations cause acute myeloid luekemia
what are the FLT3 inhibitors?
midostaurin - 1st gen
crenolanib - 2nd gen
quizartinib - type 2
what is the philadelphia chromosome?
it is demonstrable in 95% of chronic myeloid leukemia
what are drugs used for BCR-Abl translocations?
imantinib
ponatinib
