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0:00
My name is Daniela Krause from
Massachusetts General Hospital in Boston,
and I'm going to talk about small molecule
inhibitors of receptor tyrosine kinases.
Since the arrival of imatinib up for the
treatment of chronic myelogenous leukemia
in 2001 the use of other small
molecule inhibitors of tyrosine
kinases has experienced increasing
popularity over the last few years.
This really is the great story of the
successful translation of findings from
basic research to clinical medicine, but
also poses the question about
the future of modern medicine.
0:34
Tyrosine kinases belong to large group
of protein kinases they're enzymes that
can transfer a phosphate group from ATP
to a tyrosine residue in a protein.
The human genome contains
90 tyrosine kinases and
43 tyrosine kinase like genes,
they regulate cellular proliferation,
survival, differentiation,
function and motility.
They have largely been ignored for the
last 25 years in drug development because
of paucity of evidence for
a causative role in human cancer and
concerns about drug specificity and
toxicity.
But since the arrival of imatinib,
it was realized that tyrosine kinase
inhibitors can be used in specific cancers
in which a mutation that causes certain
tyrosine kinasaes to be
constitutively active.
1:21
Tyrosine kinases catalyze the transfer of
phosphate, as you can see on the top left
from ATP onto tyrosine residues, as you
can see on the top right onto proteins.
1:33
Two classes of tyrosine kinases exist.
Receptor tyrosine kinases and
non-receptor tyrosine kinases.
Nonreceptor tyrosine kinases
lack transmembrane domains, and
