Term
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Definition
| Molecules that bear resemblance to normal metabolites, and are able to interfere with cellular processes |
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Term
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Definition
| Antifolates, antipyrimidines, antipurines |
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Term
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Definition
Member of B vitamin complex
-3 Parts: Pteridine ring system, PABA, and glutamic acid |
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Term
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Definition
Additional glutamate residues
- increase the MW and also overal - charge, diminishing efflux from the cell |
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Term
| Primary Role of antifolates |
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Definition
| Carry a single carbon entity (CH3, CH2, CH2OH, CO2H, CHO) at N5 or N10 position |
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Term
| Dihydrofolate Reductase (DHFR) |
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Definition
| Converts/Activates Folic acid in the cell |
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Term
| Methotrexate (MTX, amethopterin) |
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Definition
-Acute lymphocytic leukemia in kids
-choriocarcinoma, breast cancer, osteogenic sarcoma
-psoriasis, RA
-POTENT INHIBITOR OF DHFR (antifolate) |
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Term
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Definition
close analog of folic acid, first drug to demonstrate effectiveness in acute leukemias.
-TOXIC, led to Methotrexate |
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Term
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Definition
2 Steps involving folate derived enzymes:
STEPS 3 AND 9.
Donates an aldehyde group to GAR and AICAR |
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Term
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Definition
Block DNA & RNA synth, possibly initiating apoptosis
-MOST EFFECTIVE DURING S PHASE (cell cycle specific)
Blocks Synth of Thymidine (only in DNA) |
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Term
| Leucovorin (N5formyltetrahydrofolate, citrovorum factor, folinic acid) |
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Definition
Tx osteogenic sarcoma and acute leukemias
-Often given in combo with MTX |
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Term
| Leucovorin Rescue Therapy |
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Definition
Giving potentially lethal dose of MTX to block reduced folate synth. in normal and neoplastic cells
-Giving it rescues normal cells(poor transport into cancer cells) |
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Term
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Definition
1. Impaired transport into cells
2. Altered forms of DHFR w/Decreased affinity for MTX
3.Increased [DHFR]
4. Decreased ability to synth MTX polyglutamates
5. Decreased thymidylate synthetase (TS) activity |
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Term
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Definition
Mesothelioma and non-small cell lung cancer
-antifolate, inhibits TS and DHFR
-Major toxicity = Myelosuppression; take B12 and Folic acid daily |
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Term
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Definition
A folate analog, Primary Mech = inhibit DHFR
- Peripheral T-Cell lymphoma |
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Term
| 5-Fluorouracil (5-FU, Adrucil, Efudex) |
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Definition
First Pyrimidine Antagonist
-IV admin, used in combo for GI and breast cancer
-Severe disruption of DNA function and initiation of apoptosis |
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Term
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Definition
| Precursor of FdUMP, used by cont. infusion into hepatic artery for Tx of metastatic carcinoma of the colon. |
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Term
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Definition
Prodrug of 5-FU
-Orally used for Tx of metastatic breast cancer in pts who don't respond to others (taxol and anthracyclines)
Good for tumors w/high thymidine phosphorylase activity |
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Term
| Cytarabine (cytosine arabinoside; ARA-C) |
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Definition
pyrimidine based antimetabolite
- used in acute myelocytic leukemia
-Activated by conversion 1st to the 5 monophosphate neucleotide (ARA-CMP)
-Liposomal prep (DepoCyt) for intrathecal use |
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Term
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Definition
-Cytidine analog
Front line Tx pts with metastatic pancreatic cancer and non small cell lung cancer.
- Also for melanoma and ovarian cancer
-Converted to 5-Di and Tri-phosphates |
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Term
| Gemcitabine--> 5 Di and Tri-phosphates |
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Definition
Potent inhibitor of ribonucleotide reductase
Tri->weak inhib of DNA polymerase |
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Term
| 6-Mercaptopurine (6-MP; Purinethol) |
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Definition
Purine antagonist
-a sulfur analog of hypoxanthine, whose ribonucleotide IMP is a key inntermediate in biosynth of purines
-Acute Lymphocytic leukemia |
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Term
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Definition
sulfur analog of quanine in which the 6-OH is replaced by 6-SH
- Used in Tx of acute granulocytic leukemia |
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Term
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Definition
the enzyme HGPRT is an essential component
- Purine Bases are metabolically recycled |
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Term
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Definition
| Major excretion product of purine metabolism |
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Term
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Definition
| Major excretion product of mercaptopurine metabolism |
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Term
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Definition
an anolog of hypoxanthine, and is a powerful inhibitor of Xanthine oxidase
-Blocks conversion of 6MP to 6thiouric acid, used in Tx of gout. |
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Term
| Thiopurine Methyltransferase (TPMT) |
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Definition
Low in about 1 in 300.
-Deficiency can experience severe toxicity (myelosuppression, diarrhea, mucositis) with normal doses of 6MP.
-Genetically screen pts |
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Term
| Pentostatin (Nipent, 2'deoxycoformycin) |
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Definition
from cultures of Streptomyces antibioticus
-A transition state analog in conversion of adenosine to inosine by adenosine deaminase (ADA)
-HAIRY CELL LEUKEMIA |
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Term
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Definition
Adenosine to Inosine
-inhibition by pentostatin leads to accum of intracellular adenosine and deoxyadenosine, which can inhibit ribonucleotide reductase. |
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Term
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Definition
purine analog resistant to action of ADA
-IV for use in hairy cell leukemia (Preferred drug)
-Moderate effective in progressive MS; produces DNA strand breaks and apoptosis |
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Term
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Definition
closely related to antiviral viarabine
-more stable to ADA, IV admin.
-Chronic lymphocytic leukemia |
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Term
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Definition
| Tx of peds with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens. |
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Term
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Definition
| Approved for Tcell acute lymphoblastic leukemia and T cell lymphoblastic lymphoma that has not responded to or relapsed following at least 2 chemo Tx |
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Term
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Definition
Conversion of ribonucleotides to 2'-deoxyribonucleotides, a rxn vital to DNA synth.
-ONLY ACTS ON NUCLEOSIDE DIPHOSPHATES (not mono or tri) |
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Term
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Definition
| Ribonucleotide reductase inhibitor (The 5-Diphosphate metabolite) |
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Term
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Definition
Ribonucleotide reductase inhibitor
-Used orally in chronic myelocytic leukemia, polycythemia vera, and essential thrombocytosis
-Also approved for use in sickle cell disease |
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