Anti-metabolite (hypoxanthine mimicker) that inhibits PRPP aminotransferase

-inhibit de novo purine synth

*catalyzed by HGPRT

Works by (-) feedback of PRPP amidotransferase

*metabolized by xanthine oxidase (use allopurinol)

Anti-metabolite (inhibits DHFR) thus inhibit purine and thymidylate synthesis

-Gets polyglutamated to activate (^ anti-thym synth and keeps it in the cell)

*Leucovorin used to rescue cells

Contra: Extra water mass

Anti-metabolite (hypoxanthine mimicker) that inhibits PRPP aminotransferase

-inhibit de novo purine synth

*catalyzed by HGPRT

incorporated into DNA and RNA

*Tumor lysis syndrome

-xanthine oxidase (Tx: allopurinol)

Purine anti-metabolite

-phosphorylated intracellularly to triphos, incorporated into DNA and causes chain termination

*activates apoptosis

Tx: CLL

Pyrimidine antimetabolite

-has to be phorsphorylated

-in the presence of THF binds to thymidylate synthase and traps enzyme in intermediate step

*enhances toxicity with leucovorin

*radiation sensitizer

Pyrimidine anti-metabolite used in AML

-must be phosphorylated

-Incorporated into DNA and inhibits DNA polymerase (only effective during S-phase)

Pyrimidine anti-metabolite

-phosphorylated

-Inhibits ribonucleotide reductase, causing depletion of dNTP pool

-Incorporated into DNA causing strand termination

*Potent radiosensitizer and shouldn't be used with radiotherapy

Antimetabolite

-Active by itself

-Inhibits ribonucleotide reductase, depleting dNTP, arresting cells @ G1/S (more sensitive to radiation)

Antibiotic anti-cancer

intercalates into G-C rich regions, can inhibit DNA synth

*produces free-radicals

Antibiotic Anti-Cancer

G-C rich regions, depression DNA, RNA, & protein synth

*Lowers Ca²⁺ in pts with hypercalcemia

Anthracycline antibiotic Anti-Cancer

Stabilizes topoisomerase II & generates free radicals (^ apoptosis)

*can turn pee bright red

Contra: Cardiac dx (has cardiac toxicity)

Anthracycline Antibiotic anti-Cancer

Stabilizes topoisomerase II & generates free radicals (^ apoptosis)

*dont use with impaired liver

Antracycline derivative antibiotic Anti-Cancer

-inhibit topoisomerase II

*less nausea and vomiting than doxo daunorubicin

Antracycline derivative antibiotic Anti-Cancer

-inhibit topoisomerase II (limited free radical production)

*less nausea and vomiting than doxo daunorubicin

Antibiotic Anti-Cancer

-DNA binding and DNA scission (binds Fe⁺⁺)

**may lead to pulmonary fibrosis (due to low bleomycin hydrolase in lung and skin..hyperpigmentation)

Antibiotic anti-CA

-Reduced in hypoxic environments (produces free radicals)

-Causes cross-links

Anti-mitotic anti-CA

-Bind B-tubulin and block polymerization with a-tubulin (causing depolymerization)

Anti-mitotic anti-CA

-promotes polymerization of microtubules (forms abnormal structures)- G2/M

*^ expression of P-glycoprotein=resistance

Anti-mitotic anti-CA

-promotes polymerization of microtubules (forms abnormal structures)- G2/M

*^ expression of P-glycoprotein=resistance

Anti-Cancer

*bind and trap DNA topoisomerase II

Anti-Cancer

*bind and trap DNA topoisomerase II

Anti-Cancer

Topoisomerase I inhibitors

*causes double stranded break when rep fork catches it

Renal Clearance

Anti-Cancer

Topoisomerase I inhibitors

*causes double stranded break when rep fork catches it

Prodrug

*Some lymphoid tumors lack ability to synth L-asparagine

*can cause allergic rxn

Nitrogen Mustard (alkylating agent)

-Forms cross-links

Nitrogen Mustard (alkylating agent)

-Forms cross-links

*requires metabolic activation in liver

Sfx: hemmorhagic cystitis (by acrolein)

*Use Mesna

Nitrogen Mustard (alkylating agent)

-Forms cross-links

*designed derivative

Orally active Nitrogen Mustard (alkylating agent)

-Forms cross-links

Sfx: GI upset and hepatotoxicity

Nitrosurea

anti-CA used for brain tumors (lipophilic)

*can cause severe delayed myelosuppression

Nitrosurea

anti-CA used for brain tumors (lipophilic)

*can cause severe delayed myelosuppression

Nitrosurea

anti-CA used for brain tumors (lipophilic)

*can cause severe delayed myelosuppression

and delayed renal failure in children

Nitrosurea that methylates @ O-6 (not N7)

-monofxnal, can be carcinogenic

AntiCancer

causes DNA methylation, plasma t1/2= 7 mins

*monofxnal=highly carcinogenic, can cause infertility

Platinum complex

-undergo sequential aquation, causes intrastrand adducts

Sfx:Ototoxicity

Platinum complex

-undergo sequential aquation, causes intrastrand adducts

Sfx:Ototoxicity

Steroidal antiestrogen, binds E₂R causing downregulation

2nd line tx

all-trans retinoic acid

APML

Tyrosine Kinase inhib

CML (Bcr-Abl)

EGFR Tyrosine Kinase inhib

NSCLC

EGFR Tyrosine Kinase inhib

 SCLC