2016
cytotoxic agents
Cell Cycle-nonspecific (CCNS) agents Alkylating agents Carmustine Chlorambucil, Melphalan, Cyclophosphamide, Thiotepa Anthracyclines Daunorubicin, Doxorubicin, Epirubicin Antitumor antibiotics Mitomycin Platinum analogs Carboplatin Cisplatin Oxaliplatin
Cell cycle nonspecific (CCNS) agents S (2-6h) G 2 (2-32h) M (0.5-2h) G 1 G 0
Cell cycle specific (CCS) agents
Cell cycle-specific (CCS) agents Antimetabolites (S Phase) 5-Fluorouracil (5-FU) Methotrexate (MTX) Topoisomerase II inhibitor (S-G2 phase) Etoposide Taxanes (M Phase) Docetaxel Paclitaxel Vinca alkaloids (M Phase) Vinblastine, Vincristine, Vinorelbine Antitumor antibiotics (G2-M Phase) Bleomycin
Antimetabolites S
(methotrexate, MTX) (DHFR) dtmp DNA
(fluorouracil, 5-FU) dump dtmp
mercaptopurine 6-MP
hydroxycarbamide, HU
cytarabine, Ara-C DNA
Antimetabolites 1 2 3 4 5 DNA
DNA DNA (topoisomerase) DNA DNA DNA DNA (topoisomerase)
DNA
+DNA- DNA DNA
Alkylating agents (nitrogen mustard) (Cyclophosphamide) (Thiotepa, Riethylene, Thiophosphoramide TSPA) (Busulfan, (Carmustine,,
DNA A Cisplatin Carboplatin Oxaliplatin
cisplatin,,ddp DNA
bleomycin, BLM DNA, G2
(topoisomerase) camptothecin, CPT DNA : S : DNA I
Etoposide, VP16 DNA II S G2
teniposide, VM-26,
D
doxorubicin, ADM RNA
M Vinblastin : Vincristine :
Paclitaxel M
Docetaxel
Harringtonine Homoharringtonine
L-ASP
1. 2.
Hormone Drugs For Prostate Cancer Class Antiandrogens Drugs (flutamide) Function & target Androgen (testosterone) antagonist & uptake inhibitor GnRH Agonists goserelin (leuprorelin) Decreased androgen or estrogen production Estrogens (diethylstilbestrol) Estrogen receptor agonist; antagonizes androgens
Hormone Drugs For Breast Cancer Class Drugs Function & target Cancer Androgens (methyltestosterone) testosterone propionate fluoxymesterone Aromatase inhibitor, testosterone receptor agonist Breast GnRH Agonists goserelin (leuprorelin) Decreased androgen or estrogen production Prostate & breast Antiestrogens (tomoxifen) toremifene Estrogen receptor antagonist; prevents tumor growth stimulation Breast Aromatase Inhibitors (Anastrozole) (letrozole) Reduces levels of circulating estradiol Advanced breast cancer (aminoglutathimide)
EGFR tyrosine kinase inhibitors Gefitinib Anti-EGFR mabs Trastuzumab ATP TK TK
Trastuzumab (Herceptin): Humanized Anti-HER2 Antibody HER2 epitopes recognized by hypervariable murine antibody fragment Human IgG-1 Targets HER2 protein High affinity (K d = 0.1 nm) and specificity 95% human, 5% murine Decreases potential for immunogenicity Increases potential for recruiting immune effector mechanisms Monoclonal antibody targeting of HER2 growth factor receptor is the first FDA-approved use of biologic therapy in breast cancer
Gefitinib Trastuzumab Her2+
VEGF Signal Inhibition bevacizumab Tumor VEGF Rh-Endostatin Angiogenesis
Imatinib (Gleevec ) Competitively inhibits tyrosine kinase activity of BCR-ABL BCR-ABL tyrosine kinase is present in virtually all patients with chronic myelogenous leukemia (CML) and some patients with acute lymphoblastic leukemia (ALL)
Rituximab: a mouse/ human chimeric anti- CD20 monoclonal antibody CD20 Malignant B-cell Killer Leukocyte ADCC CD20 Direct induction of apoptosis Complement CDC Adapted from Male D, et al., Advanced Immunology 1996: 1.1 1.16
bortezomib 26S (potent, selective, and reversible 26S proteasome) multiple myeloma multiple myeloma
all-trans retinoid acid ATRA acute promyelocytic leukemia, APL active in patients with acute promyelocytic leukemia (APL) (RARα/PML) induce terminal differentiation
(As2O3) (As2O3) induce differentiation through degradation of the chimeric PML/RARa protein
2
1 2 3. 4.
Life cycle of malaria parasites
1 1 2 3
1~2 1 200~700 10~20 chloroquine 25
1 chloroquine
chloroquine ph Hb DNA DNA- DNA RNA
chloroquine
chloroquine 2 3
chloroquine
quinine
quinine
quinine
artemisinin artemisia annua L.
artemisinin 30% 10%
artemether artesunate
2 primaquine
primaquine G-6-PD G-6-PD NADPH, H + NADP + GSSG GSH γ-glu-cys-gly) G-6-PD NADPH GSSH GSH NADPH
3 pyrimethamine
pyrimethamine
4
2 metronidazole 1 2 3 G + G - 4 90
metronidazole 1 2 3 tinidazole ornidazole
emetine dehydroemetine
emetine dehydroemetine
diloxanide
chloroquine
/
3. pyquiton praziquantel
pyquiton praziquantel
4. mebendazole b-
mebendazole