Oncology Med Chem Pharmacology Flashcards
-tinib
Small molecule
Enzyme kinase inhibitor
Modifies cellular signaling
Chemical synthesis
100% pure defined structure
Can take orally
Targeted (signal based) therapies
HAG SINS TTZ
Herceptin Avastin Gleevec Sutent Iressa Nexavar Sprycel Tarceva Tykerb Zactima
-mab
Monoclonal antibody
Biologic
Works on receptor to modulate cell signaling
Living cells and cell lines
Heterogenous complex structure
Injected
Less stable and sensitive to denaturation
Purines
Two rings fused
Guanine
Adenine purines
2GAPurines
Pyrimidines
One ring
1CT pyramid
Cytosine
Thymine
Guanine
GC3
Double bond O purine
3 Hbonds
ONN
Adenine
3 nitrogen purine
2 Hbonds
Cytosine
Double bond O Pyrimidine
3 Hbond
ONN
Thymine
Two double bond O pyrimidine
2 Hbonds
Go
Growth factors - EGF, VEGF
Oncogenes - ras
Stop
Tumor suppressor genes
P53
Purine biosynthesis
GGACT
Glycine Glutamine Aspartic acid Cofactor THF CO2
6-MPRP
Mercapto-purine-ribose-phosphate
From 6-MP prodrug
Deplete PRPP stores
InosineMP mimic
Methotrexate
Works and interferes wherever THF cofactors is active
Purine antagonists
Fake nucleoside mimic
Competitively inhibit DNA polymerase
Vidarabine
Fludrabine
Cladribine
Pentostatin
Adenosine Deaminase (ADA) inhibitor
Transition state analog mimic
Prevent breakdown of vidarabine and other nucleoside mimics
Adjunct therapy
Xanthine oxidase inhibitor
Inhibit xanthine (from guanine and adenine) from oxidizing to Uric acid and causing gout
Tumors with high EGFR expression
NSCLC - non-small cell lung cancer
Prostate
Gastric
Breast - HER2 human EGFR
HER2
Human EGFR,
Active as homodimer
Herceptin (trastuzumab) flags for immune cell destruction and blocks downstream HER2 signaling by preventing dimerization of HER receptors
Iressa and tarceva
EGFR kinase antagonists with common anikinoquinazoline skeleton
Affinity and compete for ATP-binding site
Tarceva has key water molecule interaction
Gleevec
Bind and stabilize an inactive form
Gleevec resistance mutation
Threonine 315 to isoleucine 315
ATP can displace gleevec easier
Iressa resistance mutation
Threonine to methionine
Nilotinib
Designed against amino acid resistance
Backup for gleevec resistant tumors
Zolinza
HDAC inhibitor: Epigenetic target
Acetyl makes lysine neutral and loosens histone grip on DNA: more transcription of p53
Lysine is normally positive without Acetyl and binds tightly to DNA
Interchangeable biosimilar
FDA determined safe for substitution
Glycine
Only amino acid with no chirality
Mizoribine
IMP dehydrogenase inhibitor
Blocks XMP/guanine nucleotide synthesis
Mycophenolate
IMP dehydrogenase inhibitor and
GMP synthetase inhibitor
ADA
Amine to double bond O
Deactivated purine antagonists
SCID = ADA deficiency & lymphocyte destruction
Gout
Excess (AMP/GMP) purine catabolism
Or deficient HGPRT salvage pathway (inosine gets deaminated and later forms Uric acid)
Von gierks disease
Increase G6phosphatase
Increase PRPP for purine biosynthesis
Excess Uric acid production
Purine metabolism disorders
Increases PRPP synthetase
PRPP amido transferase
Defective HGPRT
Increase G6phosohatase
Leech-Nyhan Syndrome
HGPRT deficiency
Febuxostat
Selective XO inhibitor
Non purine
Less interactions and side effects than allopurinol
Allopurinol
Nonselective XO inhibitor
Purine analog
Rate limiting step of purine biosynthesis
PRPP to PRA
Inhibited by 6MPRP
