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33 Cards in this Set
- Front
- Back
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there are two types of kinases |
one in the cytoplasm second acts as a receptor |
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whos the cofactor if the kinase |
ATP!! |
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Nucleophile |
OH of the tyrosine |
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Electrophile |
phosphate on the ATP |
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two families |
serine + histidine |
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hydrophobic pocket |
doesnt do anything to the binding but if we inhibit it -> 3amedott |
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What does magnesium do? |
stablizes the charges on the phosphates because it has a plus charge. 2 metals 2 amino acids |
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gate keeper residue |
amino acid in the entrance to the hydrophobic pocket ( differs between kinases) |
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active receptor |
more open because of the withdrawing between tyrosine charges(phosphates)+atp open |
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type 1 inhibitors |
active |
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type 2 inhibitors |
inactive |
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inactive conformation |
is a lot different between the kinases |
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gefitinib |
type 1 egfr inhibitor has anilinoquinazoline |
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aniline in gefitinib |
hydrophobic pocket (selectivity) |
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morpholine |
far from quinazoline to not lose solvitation energy -> solubility |
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quinazoline |
adenine |
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whats wrong with gefitinib? |
undergoes metabolism by cyp450[oxidation] |
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1->how did they solve the oxidation problem for gefitinib? |
added F instead of H Cl instead of CH3 |
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solubility is low now, so what to do ? (2) |
add morpholine |
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lapatinib |
inhibits HER2 -> boob cancer
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erlotinib |
boob cancer+lung cancer |
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imatinib |
tyrosine kinase inhibitor->cml |
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imatinib does NOT |
kill the cancer cell! it just inhibits autophosphorylation + substrates phosphorlyation = specific |
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egfr inhibits vs BCR abl inhibitors |
3months vs lifetime specific to that oncogene |
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we have to take gleevic |
life time so the cancer wont come back |
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5 mutations |
CANCEROUS CELLS |
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synthesizing |
phynylaminopyrimidine 1) pyridine cycle -> affinity 2)amide-> pkc , TK 3) methyl -> kshe7ot-> specific to tyrosine kinase
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gate keeper residue mutation |
overwork it or no binding |
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SECOND GENERATION!!! |
nilo(nitrogen-more interaction) disa(12) imatinib(2) |
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more than one kinase!! |
bosutinib ->Src Bcr abl sorafenib->raf1 kinase + pgfr |
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2 GNF |
allosteric! -> 3amedot! |
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ON123120 |
substrate binding |
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soratinib |
isoxazole + phenoxy 6 months |
