Med Chem Final
Terms
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- lack normal functions for that cell type
- undifferentiated
-
cancer cells which have
moved from the original site of growth - Metastases
-
Oncogenes are
derived from - normal genes that activate cell division
-
halt cell division
and promote cell differentiation - Tumor suppressor genes
- absence of immune reactivity
- anergy
- Many oncogenes are
- kinases
- Normal genes can become oncogenes due to
-
1.) being made in excessive
amounts, 2.) mutated, or 3.) made at the wrong time of the cell cycle. - most important tumor suppressor gene
- p53
-
been found defective in
most cancers including breast and prostate - p53
-
Mutations in the tumor suppressor genes such as __ are linked to breast
and prostate cancer. - BRCA1 and BRCA-2
-
It is easier to make a drug that __ than to correct
for the __. -
inhibits oncogene function,
loss of a tumor suppressor gene - objective of most anticancer drugs is to
- halt cell growth
-
Dosing often
calculated based on a - patient’s body surface area
- is used to decrease side effects of nitrogen mustards
- Mesna
-
not an anticancer drug
itself - Mesna
- decreases irritation and bleeding of bladder caused by high mustard doses
- Mesna
- deny precursors for DNA/RNA/protein synthesis or inhibit metabolic enzymes
- Antimetabolites
-
are sources of an enzyme that degrades
(deaminates) asparagine, an amino acid needed for protein synthesis - Asparaginase and pegasparaginase
-
irreversibly inhibits thymidylate synthetase to prevent synthesis of
thymidine - 5-Fluorouracil
- a nucleotide needed for DNA and RNA synthesis
- thymidine
- Often used with leucovorin
- 5-Fluorouracil
- is a designed orally active precursor of 5-fluorouracil
- Capecitabine (Xeloda)
- must be converted to triphosphates to be active
- Nucleoside-like drugs
- cytarabine (Ara-C), gemcitabine, fludarabine (Ara-A), and nelrabine (Ara-G).
- Nucleoside-like drugs
- ara-G prodrug
- nelrabine
- an enzyme that is needed to metabolize adenosine
- Adenosine deaminase
- inhibited by two drugs - pentostatin and cladibine
- Adenosine deaminase
-
are made into nucleotide precursors that block
DNA/RNA synthesis - Mercaptopurine and thioguanine
- is a dihyfrofolate reductase inhibitor
- Methotrexate
-
given in high doses
followed 12 to 24 hours later by leucovorin - Methotrexate
- a reduced form of folate
- leucovorin
-
multitargeted antifolate that inhibits both the enzymes
folypolyglumate and dihydrofolate reductase - Pemetrexed
- Pemetrexed inhibits
- folypolyglumate and dihydrofolate reductase
- Antitumor antibiotics MOA
- intercalation
- Mitomycin MOA
- crosslinks DNA
- complex with DNA and interfere with DNA synthesis
- Anthracyclines
-
They resemble
tetracyclines, having four fused rings - Anthracyclines
-
have sugars that are necessary for entry into human
cells - Anthracyclines
- Daunorubicin, idarubicin, doxorubicin, epirubicin, and valrubicin
- Anthracyclines
- are thought to form free radicals that can destroy DNA
-
Doxorubicin-iron
complexes -
Epirubicin less __
than doxorubicin - cardiotoxic
- affords cardioprotection caused by iron free radicals.
- Dexrazoxane
- for HIV cancer
- Liposomal daunorubicin
- Vincristine, vinblastine, vindesine, and vinorelbine are
- plant alkaloids
-
inhibit microtubule
formation - plant alkaloids
- inhibit depolymerization of microtubules
- paclitaxel and docetaxel
- Topotecan and irinotecan MOA
- inhibit topoisomerase I
- both contain sugars, inhibit topoisomerase II
- etoposide and tenoposide
- a weak estrogen receptor agonist
- Tamoxifen
-
selective
estrogen receptor modulator (SERM) - Raloxifene
- enzyme that converts testosterone into estrogen
- P450 aromatase
- by tri-imidazoles, anastozole and letrazole
- P450 aromatase
-
bind iron in P450
enzymes - antifungal tri-imidazoles
- exemestane and testolactone
- Steroidal P450 aromatase inhibitors
- irreversible steroidal P450 aromatase inhibitor
- Exemestane
- limits the usefulness of testolactone to three months use
- Up-regulation of estrogen synthesis
-
disrupt estrogen
related hormone cycles - progestins
-
administered continuously to down-regulate
receptors responsible for releases of LH and FSH hormones - Leuprolide and goserelin
- LHRH antagonist
- Abarelix
-
Avoids testosterone surge and causes more
rapid medical castration - Abarelix
-
Effectiveness may decrease in time - failure detected by testosterone
level monitoring - Abarelix
- can cause life-threatening allergic reactions
- Abarelix
- used in conjunction with LHRH therapies
- Biclutamide and Flutamide
-
competes with dihydrotestosterone (the active form of testosterone) for binding to androgen
receptor - Bicalutamide
- inhibits testosterone uptake into cells and binding to receptor
- Flutamide
- Estrogen receptor agonists
- diethylstilbesterol and polyestradiol
- an estrogen nitogen mustard
- Estramustine
- lead to low estrogen levels
- estrogen receptor agonists
- lowers prostate cancer risk but can be toxic
- Selenium
- is a potential vaccine to make antibodies that attack prostate cancer
- Provenge
- targets/binds prostatic acid phosphatase (PAP) on prostate cancer cells
- Provenge
-
activate retinoic acid receptors which promote cell
differentiation or death - Tretinoin and Bexarotene
- calcium receptor agonist
- Cinacalcet
-
reduces parathyroid hormone secretion,
used to treat hypercalcemia in patients with parathyroid cancer - Cinacalcet
- must dimerize in order to be active
- Epitheleal Growth Factor Receptors