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119 Cards in this Set
- Front
- Back
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Artesunate
(MOA, toxicity, resistance) |
- found in food vacuoles
- targets sarcoendoplasmic reticulum Ca/ATPase - MOA: catalysis by Fe --> free radicals - Toxicity: only active in HIGH Fe levels; active against asexual erythrocytes - Resistance: little cross resistance w/ other antimalarials |
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Atovoquone
(MOA, Toxicity) |
- MOA: bind to ubiguone/ubiquinol sites on cytochrome bc1 on malaria
- inhibit e- transport on mito membranes --> apotosis - Toxicity: bind to sites on mosquitos NOT humans - synergistic with proguanil |
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Chloroquine (4-aminoquinolones)
(MOA, Toxicity, Resistance) |
- affects blood stage SCHIZONCIDES
- basic molecule - food vacuole - MOA: increases pH --> decrease polymerization of hemozoin (nontoxic form of heme) --> increase toxic forms of heme --> free radicals --> apoptosis - Toxicity: high affinity for food vacuole compared to plasma based on lower pH - Resistance: mutation of complex NOT allowing chloroquine to bind |
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Pyrimethamine
(MOA, Toxicity) |
- SCHIZONTOCIDE
- synergistic w/ sulfonamides - MOA: inhibits DHFR - Toxicity: greater affinity for malarial DHFR compared to mammal form |
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Proguanil
|
- blood + liver schizonticides (combined w/ Atovoquone)
- prodrug of Cytoguanil - DHFR inhibitor - synergistic w/ Atovoquone |
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Sulfonamides + sulfones
Sulfadoxine/pyrimethamine (Fansidar) Dapsone/proguanil (Lapdap) Sulfadiazine/pyrimethamine |
- PABA inhibitor + DHFR inhibitor
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Doxycycline
(MOA, Toxicity, Resistance) |
- tetracycline
- blood stage schizonicides - MOA: protein synthesis inhibitor; inhibit 30S on mRNA complex - Toxicity: affinity to parasitic 30S ribosome - Resistance: mutation of 30S ribosome; decreased affinity |
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Iodoquinol
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- luminal ambiasis
- Fe:Iodoquinol ratio = 1:2 - more toxic than Diloxanide Furorate - MOA: Fe chelation --> ROS --> lipid peroxidation --> cell death |
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Paromomycin
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- aminoglycoside
- MUST be injected - ok for pregnancy - MOA: inhibit protein synthesis - bind to 30S polysome |
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Metronidazole
(MOA, toxicity) |
- mixed: luminal + systemic agent
- MOA: ferrodoxin enzyme induces NO2 --> ROS --> lipid peroxidation --> cell death - Toxicity: selective for certain amebas |
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Tinidazole
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- against Giardiasis
- similar to Metronidazole - MOA: ferrodoxin enzyme induces --> NO2 --> ROS --> lipid peroxidation --> cell death |
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Furazolidone
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- tx against Giardiasis
- similar to Metronidazole but more toxic and less effective - MOA: ferrodoxin enzyme induces NO2 --> ROS --> lipid peroxidation --> cell death |
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Suramin
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- injected SQ
- treat African Typanosomiasis - MOA: block cyclin-dependent kinases |
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Pentamidine
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- tx African Typanosomiasis
- MOA: inhibit SAM decarboxylase; inhibit biosynthesis of polyamines |
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Melarsoprol
(MOA, Toxicity, Resistance) |
- tx African Typanosomiasis
- organoarcinal drug - MUST be IV - MOA: active uptake by purine transporter and convert to arsenoxide to react w/ sulfhydryl groups --> inhibit trypanosomal glycolysis enzymes - Toxicity: higher affinity for trypanosomal enzymes; may be toxic to human (Ar) - Resistance: mutation of enzymes |
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Eflornithine
(Difluromethylornithine - DFMO) (MOA, Toxicity, Resistance) |
- only for T.b. gamienese
- MOA: bind to ornithine decarboxylase; inhibit biosynthesis of polyamines --> suicide inhibit enzyme --> cell death - Toxicity: T.b. gambienese relies on polyamine synthesis but bc NO polyamine synthesis --> cell death - Resistance: mutation in binding to ornithine carboxylase |
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Nifurtimox
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- Chagas Disease
- similar to Metronidazole - MOA: ferrodoxin enzyme --> NO2 --> induces ROS --> lipid peroxidation --> cell death |
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Benznidazole
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- Chagas Disease
- similar to Metronidazole - NOT approved in US - MOA: ferrodoxin enzyme --> NO2 --> induces ROS --> lipid peroxidation --> cell death |
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Sodium Stibogluconate
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- Leishmaniasis
- pentavalent antimonial agent - MOA: interferes w/ glycolysis and FA metabolism of glycosomes --> inhibit ATP + GTP --> cell death |
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Miltefosine (Inpavido)
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- Leishmaniasis
- MOA: inhibit phosphatidyl choline - disrupt lipid remodeling - insect cannot keep changing glycoprotein to evade host immune system |
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Benzimidazole, Albendazole, Mebendazole, Thiabendazole
(MOA, Toxicity, Resistance) |
- MOA: bind to B-tubulin --> inhibit microtubule polymerization --> cell death
- Toxicity: high affinity for B-tubulin of worms compared to humans - Resistance: lose affinity for B-tubulin of worms |
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Diethylcarbamazine
(MOA, Toxicity) |
- MOA: hydrolysis to produce N-ethylpiperazine --> toxic activator of GABA channel --> paralysis
- Toxicity: not active in vitro, only in vivo |
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Invermectin
(MOA, Toxicity) |
- tx onchoceriasis (river blindness)
- MOA: activate Glutamate Cl- channels --> tonic paralysis - Toxicity: humans lack the Glu Cl- channels |
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Piperazine
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- MOA: induce GABA channel on Cl- channel --> flaccid paralysis
- Toxicity: simple distribution phenomenon |
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Praziquantel
(MOA, Toxicity) |
- schitosomiasis
- low doses: increase muscle activity --> muscle paralysis - high dose: damage glycoprotein coat --> expose to tegumental antigens - rapid Ca uptake to activate voltage gated Ca channels (VGCC) - Toxicity: VGCC in worms inhibit adenosine --> more Ca contraction --> paralysis |
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Pyrantel
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- activate ACh nicotinic channels --> depolarizing block --> muscle paralysis in worm
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Metrifonate
(MOA, Toxicity) |
- organophosphorus
- prodrug to dichlorvos - may help memory of Alzheimer's - MOA: inhibit acetylcholinesterase - ACh opens Na/K channel --> death of worm - Toxicity: inhibit ester and amide hydrolyases and AChE specific for species |
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Niclosamide
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- inhibit oxidative phosphorylation and/or decrease ATP activity
- loss of ATP --> cell death |
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Bithionol
(MOA, Toxicity) |
- tx fascioliasis
- MOA: inhibit nematode "activated L-serine sulphydrase" activity - Toxicity: L-serine sulphydrase only on nematodes |
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Enfuvirtide (T20)
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- binds to CD4+ --> conformation change to gp120 --> conformation change to gp41 --> inhibit viral fusion to host cell membrane
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Maraviroc (Selzentry)
(MOA, Toxicity) |
- MOA: inhibit CCRP5 binding site
- NO binding to to CD4 receptor - Toxicity: only if CD4 receptor has CCRP5 binding site |
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Lamivadine (LVD)
(MOA, Toxicity, Resistance) |
- nucleoside RT inhibitor
- MOA: convert to LVD-TP - compete w/ CTP or bind to RT to inhibit DNA synthesis - Toxicity: higher affinity for viral RT - Resistance: single AA mutation (Met to Val or Ile); possible cross resistance to other drugs |
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Adefovir Dipiroxil
|
- prodrug
- tx hepatitis B - nucleotide RT inhibitor - similar to LVD - MOA: convert to Adefovir-TP --> inhibit RT --> DNA chain termination |
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Nevirapine, Delaviridine, Efavirenz
(MOA, Resistance) |
- non-nucleoside RT inhibitors
- MOA: bind to a site NEAR RT (allosteric inhibition of RT) - Resistance: mutation on RT binding sites; possible cross resistance |
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Sequinavir, Indinavir, Ritonavir, Nelfinavir
(MOA, Toxicity, Resistance) |
- HIV protease inhibitor
- MOA: acts as transition state analog to inhibit the cleavage of Phe-Pro - Toxicity: humans lack Phe-Pro - Resistance: protease mutations; possible resistance w/ other protease inhibitors but NOT HIV inhibitors |
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Raltegravir (Isentress)
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- HIV integrase inhibitor
- MOA: inhibit Mg to prevent strand transfer between virus and DNA |
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Entecavir (Baraclude)
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- tx hepatitis B
- MOA: convert to activated 5'-TP form - inhibit HBV RT - compete w/ guanosine nucleotides at HBV RT - incorporate into viral DNA --> disrupt viral DNA elongation |
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Acyclovir, ganciclovir, famciclovir, valacyclovir
(MOA, Toxicity, Resistance) |
- DNA polymerase inhibitor
- thymidine kinase MUST be active - MOA: convert to TP-form to terminate DNA chain - Toxicity: must have specific thymidine kinases; high affinity to viral DNA polymerase - Resistance: mutated thymidine kinase |
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Cidofivor - CDV (Vistide)
(MOA, Toxicity, Resistance) |
- DNA polymerase inhibitor
- tx CMV in HIV pt - MOA: convert to DP form; compete w/ dCTP to inhibit viral DNA polymerase - MUST have TWO CDV molecules to be stop DNA elongation - Toxicity: selective for HIV DNA polymerase - Resistance: mutations of DNA polymerase |
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Foscarnet (Foscavir)
(MOA, Toxicity, Resistance) |
- tx HSV-1, HSV-2, VZV, CMV, HIV
- MOA: mimics pyrophosphate groups to inhibit the binding to DNA --> keep the d-TP form --> inhibit viral DNA polymerase - Toxicity: greater affinity to viral DNA polymerase - Resistance: point mutation of pyrophosphate binding site on viral DNA polymerase |
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Amantadine (Symmetrel)
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- inhibit Influenza viral uncoating
- MOA: block M2 in channels --> decrease acid influx --> inhibit hemaglutinin from binding to cell for agglutination |
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Zanamir (Relanza)
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- neuraminidase inhibitor
- ONLY works on OLD cells - MOA: inhibit neuraminidase --> mimic sialic acid --> no hemagluttin formation - Toxicity: only cells with neuraminidase - Resistance: mutations of neuraminidase |
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Interferon Alpha Mechanisms
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1) inhibit tcp
2) inhibit tsl from viral DNA to RNA 3) inhibit protein processing 4) inhibit viral mutation |
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Palivizumab (Synagis)
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- prevent RSV
- MOA: passive immunization of monoclonal Ab for prophylaxis |
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Fomivirsen (Vitravene)
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- tx CMV
- used for immunosuppressive - MOA: oligonucleotide inihbits mRNA maturation and protein synthesis |
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Ribavirin (Virazole)
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- tx RSV and Hepatitis C
- prodrug 1) Ribovirin-5-MP inhibits inosinemonophosphate dehydrogenase --> no XMP --> no GTP 2) Ribovirin-5-TP inhibits GTP dependent caping of viral mRNA --> inhibit tcp activity |
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Amphotericin B
(Mechanism, Toxicity) |
- polyene antibiotic
- MOA: bind to ergosterol --> internal leakage into membrane - Toxicity: fungicidal at high doses - only fungi have ergosterol |
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Caspofungin (Cancidas)
(Mechanism, Toxicity) |
- large cyclic peptide
- MOA: inhibit B-1,3-glycan synthase - lose structural integrity of cell - Toxicity: B-1,3-glycan synthase only found in fungi |
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Flucytosine (Ancoban)
(Mechanism, Toxicity, Resistance) |
- fungistatic
- used w/ Amphotericin B and Fluconazole - MOA: convert 5-Flucytosine to 5-FU by cytosine deaminase 1) convert 5-FU --> 5-FdUMP --> inhibit thymidylate kinase 2) convert 5-FU --> 5-FUTP --> inhibit RNA synthesis - Toxicity: NO cytosine deaminase in mammals - Resistance: those taking Flucytosine |
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Fluconazole (Diflucan)
(Mechanism, Toxicity, Resistance) |
- imidazole, triazole
- fungistatic; fungicidal at high doses - MOA: inhibit 14-alpha-demethylase - inhibit conversion of lanosterol to ergosterol - Toxicity: selective for fungal 14-alpha-demethylase - Resistance: oral candidiasis; mutated enzyme |
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Griseofulvin
(MOA, Toxicity, Resistance) |
- MOA: inhibit mitosis and microtubule associated proteins (MAP)
- break mitotic spindle - Toxicity: fungistatic; selective to trichophyton, microsporum, epidermophyton - affects humans at high doses - Resistance: mutation to binding site |
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Terbinafine (Lamisil)
(MOA, Toxicity) |
- systemic use
- more potent than Fluconazole - MOA: inhibit squalene-2,3-epoxidase --> decrease ergosterol synthesis - Toxicity: fungicidal |
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Amorolfine (Loceryl)
(MOA, Toxicity) |
- systemic
- MOA: inhibit 14-alpha-demethylase + delta-7,8-isomerase - Toxicity: fungistatic |
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Haloprogrin (Halotex)
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- MOA: release Iodide (known antifungal substance)
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Ciclopirox Olamine (Loprox)
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- MOA: chelete Fe ions --> ROS --> lipid peroxidation --> cell apoptosis
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10-Undecenoic Acid
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- odd chain length carboxylic acids --> antifungal activity
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Potassium Iodide
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- release Iodide
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Gentian Violet
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- induce ROS/lipid peroxidation
- antibiotic and antifungal of local infections |
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Mechlorethamine (Mustargen)
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- highly reactive nucleophile (ALIPHATIC)
- ONLY IV - ALIPHATIC amine --> interact with structure --> aziridium --> DNA cross linking |
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Bendamustine
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1) purine structure inhibits purine metabolism --> no DNA/RNA synthesis
2) cytotoxic 2-arm mustard - useful against other resistance |
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Thiotepa
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- weaker nucleophile due to double-bond Sulfur near amine
- less aziridinium form --> interstrand DNA cross linking |
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Cyclophosphosamide (Cytoxin)
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- prodrug
- high alopecia - MOA: metabolism by CYP 2B6 to form active phosphoramide mustard + acrolein - acrolein causes renal toxicity |
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Ifosfamide
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- prodrug
- MOA: metabolism by CYP 3A4 to form active NON-aziridinium + acrolein metabolite - neutralize acrolein with MENSA |
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Busulfan (Myleran)
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- alkyl sulfonates
- useful in leukemia - good LG of sulfonates by rxn by DNA |
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Lomustine
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- nitrosoureas
- prodrug - MOA: spontaneous breakdown to active aziridinium --> DNA crosslinking - lack resistance to other alkylating agents |
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Dacarbazine
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- prodrug
- DNA methylating agent - must be given IV - MOA: methylation forms methylcarbonium ion to cause DNA cross linking |
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Temozolomide
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- convert to methyliazonium ion to release Ca2+ to interact with DNA
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Procarbazine
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- prodrug
- metabolized by CYP450 + MAO to form azoprocarbazine --> alkylate to cause DNA strand break |
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Methotrexate
(MOA, Toxicity, Resistance) |
1) inhibit thymidylate synthase
2) inhibit DHFR 3) inhibit de novo purine synthesis - Toxicity: MTX uptake by same transporter as folic acid - use Leucovorin to rescue normal cells from death - Resistance: decreased uptake of MTX |
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Cytarabine
(MOA, Resistance) |
- pyrimadine analogues
- MOA: -OH functional group inhibits DNA polymerase by incorporating into DNA to stop chain elongation - converted into Ara-CTP to compete with DNA polymerase substrate - Resistance: increased cytidine deaminase activity; decreased Ara-CTP affinity for DNA polymerase; decreased uptake of Ara-CTP |
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Fluorouracil (5-FU)
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1) convert into FdUMP --> inhibits thymidylate synthase
2) FUTP inhibits RNA fxn 3) FdUTP crosslinks with DNA |
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Capecitabine
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- prodrug of 5-FU
- orally active - MOA: convert to 5-FU and cause similar mechanism 1) inhibit thymidylate synthase by FdUMP 2) FUMP inhibits RNA fxn 3) FdUTP cross links with DNA |
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Gemcitabine (Gemzar, dFdC)
(MOA, Toxicity, Resistance) |
- active metabolite after converting to dFdCDP, dFdCTP
1) dFdCDP inhibits ribonucleotide reductase 2) dFdCTP inhibits DNA polymerase 3) dFdCTP cross links to DNA and adds another nucleotide to terminate DNA chain - Toxicity: active in ALL PHASES including G0 - Resistance: inability to add extra nucleotide |
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Azacytadine
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- epigenic agent
- inhibits DNA methyltransferase - acts as suicide inhibitor |
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Decitabine
(MOA, Toxicity) |
- epigenic agent
- prodrug - MOA: convert to TP form to inhibit DNA methyltransferase - Toxicity: S PHASE specific agent |
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Mercaptopurine
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- purine metabolite
- convert to MP form to incorporate into DNA --> chain break |
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Thioguanine
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- purine metabolite
- prodrug - convert to TP form to incorporate into DNA - Toxicity: Specific for S phase |
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Clofarabine (Clolar)
(MOA, Toxicity) |
- uptake by passive diffusion or active transport
1) convert to TP by d-Cytidine Kinase (dCK) --> inhibit DNA polymerase 2) inhibit ribonucleotide reductase 3) activate capase pathways to disrupt mito membrane to release apoptosis initiator Cytochrome-C - Toxicity: Cl group prevents inactivation of adenosine deaminase --> longer drug half life |
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Pentostatin
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- tx hairy cell leukopenia
- MOA: mimics adenosine to inhibit adenosine deaminase |
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Nelarabine
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- purine nucleoside analog
- convert to arabinosylguanine-TP --> incorporate into DNA chain --> cell death |
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Hydroxyurea
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- deoxyribonucleotide reductase inhibitor
- MOA; inhibit ribonucleotide reductase - no formation of deoxy-ribonucleotide-DP --> no DNA synthesis |
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Bleomycin Sulfate (Blenoxane)
(MOA, Resistance) |
1) bind to DNA chain
2) chelate with Fe --> ROS --> lipid peroxidation --> DNA chain breaks - Resistance: increase bleomycin hydrolyase to metabolize bleomycin; initiation of DNA repair enzymes |
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Dactinomycin (Actinomycin)
(MOA, Toxicity, Resistance) |
- MOA: bind to DNA by intercalation (btwn base pairs) --> misreadsing by DNA polymerase --> inhibit DNA and RNA syntehsis
- Toxicity: favors binding to G-C base pairs - Resistance: increase efflux by MDR; many drug cross resistance |
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Mithramycin (Plicamycin)
(MOA, Resistance) |
- MOA: bind to Mg at G-C base pairs --> inhibit RNA synthesis
- inhibit mitosis and nucleic acid synthesis - Resistance: competes with dactinomycin as intercalator |
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Doxorubicin (Orthoquinone)
(MOA, Resistance) |
- daunomycin analogs
- MOA: bind to DNA to produce free radicals that inhibit topoisomerase II - Resistance: decrease topoisomerase II activity; induction of MDR; decrease cellular response to apoptosis - major cardiotoxicity |
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Dexrazoxane
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- cardioprotection against daunomycin analogs
- enter cells by diffusion (nonpolar) - chelates with Fe - Fe-drug-toxin complex diffused out of heart cells |
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Mitoxanthrone
(MOA, Toxicity) |
- similar to doxorubicin
- MOA: form paroquinone structure --> ROS --> inhibit topoisomerase II - Toxicity: less cardiotoxicity compared to others (less ROS production) |
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Mitomycin C (MMC)
(MOA, Resistance) |
- MOA: alkylation of DNA --> aziridinium structure --> DNA cross-linking --> inhibit DNA replication
- Resistance: decreased bioactivation and increased DNA repair enzymes |
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Vincristine
(MOA, Toxicity, Resistance) |
- vinca alkaloid
- high neurotoxicity - inhibit M phase (metaphase) - MOA: bind to microtubules --> disrupt spindle formation --> apoptosis - Toxicity: action ONLY at M phase - Resistance: MDR by glycoprotein p-170 induction; cross resistance to natural anticancer products; decrease binding of vinca alkaloids to tubulin |
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Docetaxel
(MOA, Resistance) |
- taxol derivatives
- inhibit M-phase - MOA: bind to microtubules at B-tubulin units --> apoptosis - Resistance: decreased binding of drug to B-tubulin; induced MDR |
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Ixabepilone (Ixempra)
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- antimitotic natural product from cellulose
- similar to doxetaxel - NO cross resistance to taxanes - MOA: bind to B-tubulin but different site than docetaxel |
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Estramustine
(MOA, Toxicity) |
- used in prostate cancer
- MOA: bind to B-tubulin and microtubule assn proteins (MAP) - possible alkylation by 2-armed mustards - Toxicity: M-phase specific |
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Irinotecan
(MOA, Toxicity) |
- camptothecin analog
- REQUIRES active DNA synthesis - MOA: inhibit topoisomerase I --> inhibit religation step of DNA that is catalyzed by enzyme - irreversible break - Toxicity: S-phase specific |
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Teniposide (VM-26, Vumon)
(MOA, Toxicity) |
- MOA: bind to topoisomerase II --> inhibit religation of double stranded breaks
- Toxicity: act on S and G2 phase |
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Imatinib (Gleevec)
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- treats chronic myeloid leukemia
- MOA: inhibits BCR-ABL TK by blocking phosphatidylinositol-3-kinase |
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Sunitinib (Sutent)
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- treat GI stromal tumors, advanced renal cell carcinoma
- MOA: NONselective (multiple) TK inhibitor - direct cytotoxic effects |
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Erlotinib (Tarceva)
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- advanced non-small cell lung cancer
- MOA: highly specific for HER1 (EGFR) TK inhibitor |
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Lapatinib
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- treat HER-2 positive breast cancer
- dual kinase inhibitor - MOA: inhibit EGFR and specifically HER2/neu |
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Trastuzamab (Herceptin)
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- humanized monoclonal antibody
- MOA: block EGFR from binding and initiating growth factors - kills immune system cells |
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Cetuximab (Erbitux)
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- treats head, neck, colorectal cancers
- combine with Irintocan - recombinant human/mouse chimeric monoclonal antibody - MOA: inhibits EGF and other ligands --> no cell proliferation, metastasis, or angiogenesis |
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Rituximab
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- treat B cell non-Hodgkin's lymphoma
- MOA: bind to human CD20 receptors --> activate Antibody Dependent Cell-mediated Cytotoxicity (NK, T cells) and Complement Dependent Cytotoxicity (complement proteins for cell lysis) --> apoptosis |
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Ibritumomab tiuxetan
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- radioimmunotherapy
- MOA: chelate to Y-90 (high energy beta emitter) --> complex binds to CD20 --> emit radioactivity to kill cells |
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Bevacizumab (Avastin)
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- antiangiogenic
- antiproliferative - pro-apoptotic - block VEGF --> no angiogenesis --> tumor death |
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Bortezomib (Velcade)
(MOA, Toxicity, Resistance) |
- treat multiple myeloma
- MOA: inhibit 26S protease activity --> proteolytic acivity --> cell death - possible ROS and cytochrome C release - Toxicity: only affects 26S proteosome in humans - Resistance: mutations of 26S |
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Temsirolimus
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- treat renal cell carcinoma
- MOA: inhibit mTOR pathway --> no IL-2 production - Toxicity: G1 cell arrest; mammalian target of Rapamycin - Resistance: mutation of mTOR |
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Lenalidomide
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- lacks teratogenic effect of thalidomide
1) 50000x greater potency at inhibiting cytokine (TNF-alpha) and IL-6 compared to thalidomide --> no angiogenesis 2) inhibits anti-apoptosis of cell growth 3) inhibits IL-6 to limit adhesion 4) stimulate NK cell production and functionality |
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Tretinoin
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- agonist of retinoid receptors (RAR-alpha) to stimulate differentiation of cancer cells
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Vorinostat (Zolinza)
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- histone deacetylase inhibitor
- acetylates LYS residue to allow DNA tcp - induces differentiation, cell cycle arrest, apoptosis - synergistic with trastuzumab |
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Aromatase inhibitors
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- treat breast cancer
- inhibit the conversion of androstenedione to estradiol |
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Fulvestrant
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- DIRECTLY block estrogen receptor
- no agonist effects --> PURE antagonist - better than tamoxifen |
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Flutamide (nilutamide, bicalutamide)
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- treat prostate cancer
- MOA: competes with testosterone to bind to androgen receptors |
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Eltrombopag Olamine
|
- increases platelet counts
- decreases bleeding of chronic idiopathic thrombocytopenia purpura - MOA: small molecule thrombopoietin receptor agonist --> stimulate IL-2 and IL-12 --> stimulate cell differentiation |
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Levamisole
|
- low side effects
- use w/ 5-FU and interferon for colon cancer - MOA: small molecule drug to decrease corticosteroid production --> remove corticosteroid immunosuppression - restores cells that were lost |
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Telomerase Inhibitor
|
- prevent the cancer cells from maintaining chromosome length by inhibiting the cancer's human telomerase RT (hTERT)
- no lengthening of cancer cells --> cell death - lack of telomerase actually beneficial in normal and aging cells --> protect against cancers |
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RNAi (silencing RNA, siRNA)
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- DICERS cut the dsDNA into shorter sequences (30 bp)
- insert antisense RNA into mRNA --> mRNA cleavage + tsl arrest --> silencing of a gene |
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Tankyrase
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- "indirect" telomerase inhibition
- packages the DNA to be less susceptible to telomerase |
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Activation of Death Receptors
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- activation of high levels of TNF
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Two pathways of TNF
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- selection of pathway depends on the dose of drug
1) inflammation, anti-apoptosis, proliferation 2) mitochondrial apoptotic pathway |
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Apo 2L/Trail ligand
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- TNF-apoptosis-inducing ligand
- activates with death receptors (Trail) - release caspase 8 which interacts with type 2 cells --> stimulate BiD --> apoptosis |
