Oncology begining Flashcards
Semi-synthetic Estrogen preparations
5- Fluorouracil Inhibits?
What is its mechanism
What type do drug is it?
Sensitive to?
Toxicities? 5
Blocking the Metabolism of 17a-Hydroxyprogesterone
Estrogen preparations: Natural estrogens and their esters
Structure activity relationship of Estrogens
What nucleus with what type od A ring?
3-Hydroxy group
- Metabolism of this?
- What is used to block this
Then 17bhydroxyl group
Mitomycin: DNA Alkylating Agent
MOA:
- Inert until? Generates what?
- What else is generated that can damage the DNA?
Unstable to?
What colored excretion?
Forms?
Natural Estrogens: Estradiol
Amongst the natural?
Metabolic vulnerability?
Forms?
Chlorotrianisene
What type of drug? Agonist or antagonists and for what hormone?
No free ___ which blocks what? This also means it can be what form?
Distance of what?
What are the biosynthetic steps for Estradiol from Androstenendione
—> Aromatase gives Estrone
17b-HSD —> Estradiol
Trastuzumab/HER2
Prototypical Example of Drug targeting what factor?
Humanized what?
Strategy for this drug?
Heterodimer of this Receptor triggers?
This is all talking about cancer not really the drug but the reason for the drug
Megesterol Acetate
(Megace)
What on the B ring increases activtiy?
How much of oral dose is metabolized?
How does it differ from Medroxyprogesterone?
How does it block metabolism
DNA methyltransferase inhibitors
3
DAN
MOA
19-Norandrostane Derivative products
SAR
19-nortestosterone
What does the NOR mean?
What type of effect does this favor then?
Phytoestrogens
Soy isoflavone B-glycosides are?
Methyltestosterone
What are its featureS?
What block oxidation at 17 keto
Activity compared to testosterone? An improvement is?
androgenic or anabolic?
what metabolism?
Imatinib
Prototypical Small Molecule Kinase Inhibitor
MOA
Inhibits what growth factor and what kinase?
Anabolic Agents
flow chart
Androgenic + anabolic agents
flow chart
Nibs are inhibitors of?
Distinct chemical structure facts
6 Drug interactions, Mutations, distinct __ interaction, Dustinct ___ profiles, Distinct ___ - ___ interactions
Norethindrone Acetate Combipatch
Ester __? Metabolized where to form?
Prolonged action in what form?
Oxandrolone
WHat blocks 17 keto? what else does this do form wise?
What is going on wiht the A ring?
what form?
Ither Kinase Inhibitors
Androstane Nuc
what are the parts?
What 4 carbons are important for the 19-norandro derivatives
5a-Reductase where does it act?
what is its product formation with testosterone?
Ethisterone and Analogues
_ derivative of what?
SAR summary of Progesterone and Derivatives
Progestational effects depend on wha 4 things
What mays it fit better to the receptor?
Alkene
Progesterone
Prometrium
Duration? Due to?
Where from?
What places are susceptible for metabolism?
MonoclonalAntibodies vs. Kinase Inhibitors
Kinase
- Cytosolic vs. ?
- REversible vs?
- ____ target
Monoclonal
- Extracellular what region of ?
*
Synthetic Estrogenic Agonist
DES
A very ____ ____ estrogen
What Isomer is 10 x more potent than?
Formerly used to?
Now?
Raloxifene
What type of activity? And what two things does this help?
What effect on breast tissue?
No ___ effect on the uterus?
form?
MAB with a warhead
Desogestrel
Progesterone
Progestasert
Despite?
What does the 17 ethynyl 19-Norandrostane do ofr activity across the board?
SAR Summary of Progesterone and Derivatives Synthetic Mods
2 main mods and talk about their effects
Estrogens: 17 a group hydroxl
What happens at the 17b group and what enzyme causes it?
Hepatic oxidation by 17b-hydroxysteroid dehydrogenase
Makes a less active ketone and limits oral activity
Where is the focus of progesterone drug in the pathway?
Chemotherapy targets
- Combine the selectivity of ___ ___ inhitors with the potent action of another class
- Are generally broad in spectrum and can be moderately toxic
- Are useful for the metastic cancers but are nonselective and have many side effects
- Are more selective and generally less toxic
- Are more selective and have varying levels of toxicity
- Draw the picture of where they act
There are now proposed cancer hallmarks
Emerging hallmarks and Enabling characteristics
4
Progestin Products: Progesterone and Derivatives
Starting at Nat Progestins then from there
Anastrozole
Specific?
Tx of?
Where is 17a-Hydroxyprogesterone in the Steroid Hormone Syn pathway
Medroxyprogesterone Acetate
at teh C6 position ___ is added and this decreases?
This blocks?
Intelligent therapy
Selective estrogen Receptor Modulators
SERM
What are these trying to circumvent
Stanozolol
What does it contain?
blocks oxidatio?
forms? What type of activity?
Topo I and II slide
Role of the cell cycle in chemotherapy
What controls cell cylce phase transitions? Failre causes?
Control growth and differentiation of targeted distant cells
What controls only nearby cells?
Coming from the cell itself?
Cells in what phase are least senstive to drugs?
Many drugs have what type of selectivty?
Tamoxifen and Raloxifene
Which one requires activation?
Progestin Products: Progesterone Derivatives
3
Epothilones
Complement what other drug?
MOA?
Improved?
What do you not need?
Chemical Stability
19-Norandrostane
SAR at c17 what is added and what does it block?
Analogues with what are inactive?
AntiAndrogen Chart
Anthracyclines DNA intercalation
5 of them all end with
2 MOA
Red quinones
Rings strucvute gives it away
Cholane?
Small sidechaine than cholestane 4 carbons
two methyls 18 19
Estrane nucleus has no?
C19 carbons
Testosterone esters
longer the chain longer the?
What type of drugs are they?
what is inhibited?
Miscellaneous: Bleomycin-Oxidative Cleavage of DNA
MOA
SE
Pregnane nucleus what are the important features? For derivates
Etheyleneimines
ThioTEPA
MOA:
Selectivtiy
Activated in?
Deactivation?
Active in the?
Medroxyprogesterone Acetate
What SC is introduced? What does this cause?
Slow reduction of the keto and double bond 4-5
Saw palmetto
BLM-Fe Complex
Damages DNA via?
Rescue therapy for methotrexate
Toxicity of Methotrexate
Hallmarks of Cancer
6 well defined hallmarks
Tretoin: Differentiation Therapy
MOA?
SE? Important notes
testosterone esters are subject to?
What is there physiological concentration like?
admin?
Activations of Capeitabine
Prodrug
Selectivity
SE profile
Additional considerations on therapeutic txs
What is necessary so a patient has the best chance of survival?
What is particularly dangerous?
- This puts stress on?
- How the these treated?
How long does it have to be to be a new cancer?
Cure means?
Practice
Letrozole
What does it do?
Tx of? Second line to?
Progestin Products
19-Norandrostane Derivatives
The rapid metabolism of progesterone triggered?
Esterified estrogens
Estra-cyp
Mutations and Biochemical Basis of Cancer
Many paragraphs
Most commonly cancer is caused by what type of mutations?
What is used to rationalized the difference between initiation and transformation?
So whats the deal with increasing age and cancer?
Biclutamide
Administered as a?
what enantiomer is inactive?
What does it bind to?
Role of aromatase?
Dienestrol (Synestrol)
What has been maintained?
Active in what wat? But how is it used primarily?
esterogen group at 3 position?
Subject to?
What does this limit?
- Phenolic hydroxyl
- Subject to biotransformation, which limits the duration of action, sulfation and glucuronidation
Estrogens 17 alpha ethinylation
Blocks?
Permits?
Number the cholesterol
Androstane
Fluoxymesterone
Bloicks what?
what makes it 5-10x more potent than testosterone?
Other Platinum Metal Complexes
Carboplatin and Oxaplatin
MOA?
STructural changes 2
Why does this make them better?
Carboxylic acid improves the safety profile and the
Cyclohexan 1,2 diamine overcomes resistance and once it gets to the right site it is more toxic
These drugs have different toxicities so onces put into a cocktail can get complement toxicities
Saw palmetto
Taxanes
MOA
Distinct
Lipophilicity and Implications
Moderately lipophilic need Emulsfying agent
Conversion of dUMP to dTMP
Phytoestrogens
What activity do they have?
The two hydroxyl groups?
Antiandrogenic peptides
Leuprolide
Goserelin
These drugs contain what?
GnRH
Incorporation of D AMino actids helps this
Classic Chemotherapy and the Cell Cycle
Hallmarks
- What must the drugs do?
Kinetics of Cell Division
- How can processes occur in cancer cells?
- Drugs can?
Classical Agents
- How do they interfere with these processes
Newer Agents
- Interfere with what pathways?
- Inhibit signals associated with? What type of cells?
Selectivty
For each class consider what?
Notes: How do tumor cells grow? How do cocktail target them?
Picture
Terminal Differentiation—>?
Phases of the cell
Tamoxifen
What isomer is used? What type of compound is it?
Used to treat?
form?
Retinoid Therapies to Stimulate Differentiation
Triphenylethylene Analogs
What structure is retained? But features what type of moeity that is critical for antiestrogenic activity?
Epipodophyllotoxins: Inhibition of?
Teniposide is more lipophilic more distribution more potent you can have less drug to get same effect
Dutasteride
What does it do?
and how
forms?
17a-Methyltestosterone
What are the key features?
What is blocked?
What does this mean for the drug?
General Notes about N-Mustards
MOA
- What generates an active electrophile and what does this react with? What is the fast and slow process
- What leads to mutation of DNA? And what is the mutation?
- What are the two steps prior to chain fragementation and destruction of DNA
- What is more difficult to repair mono or bi alkylation?
- How does deactivation occur?
- Selectivity Occurs from?
- Selectivity and Activity are Influences by?
- What are group is more reactive?
- How is potency influenced?
- Two ways that aziridinium formation is depressed?
- Prototype Mechlorethamine
Leuprolide and Goserelin DisruptEndogenous Hormonal Feedback systems
Action of Androgenic Peptides
- Stimulates
- Increase
- Initially
- Loop?
- Deprive tumor of?
SAR
19-Nortestosterone derivatives
What effect predominate and why?
A combination of what two things provides and overall ____ effect?
Fluoxymesterone
Androgen or anabolic acitivy?
more resistant to?
Nitrosoureas: Prodrugs
Carmustine
MOA?
Instability
Log P?
It is fragmented into twon parts what are they? They are the active DNA parts
How is this drug prepared for use?
Vinyl Cation and the 2-Chloroethylamine so you are mutating DNA at two sites
Nandrolone Decanoate
Absence of? gives it what activity?
what form?
Substitution with EWGs attenuate reactvitiy in what way?
P=?
This provide a similar activity to?
What are the drugs/
Th
Abx and higher derived natural products
3 classes
Topoisomerase Inhibitors
Mitosis Inhibitors
Msc
Dactinomycin: DNA Intercalation
MOA?
DMPK thing cyclic amides
Estrane nucleus
Absence of 19 carbon
Topoisomoerase Chane the State of?
Why is this a good target?
17a-Hydroxyprogesterone what is it?
Where is it produced?
Bitransformation of testosterone?
What is the primary route for inactivation?
THG article
C13 Ethyl Derivatives
All have what at C13?
All haev what at C17
Pregnane
Much smaller side chaine
Ketoconazole: Antiandrogen and?
MOA
Cytarabine
What is its major structural change?
How does it work?
MOA?
- Ribose to Arabinose
- Intracellular kinases phosphorylate to ARA-CTP very polar and cannot leave the cell
- ARA-CTP inhibits DNA and RNA polymerases and nucleotide reductases
Nilutamide
Absorbed where?
Hydantoin analof that blocks?
Oncogene and Cytokine Antagonists
1 Mature
2 tumor
Triazole ___ inhibitors
2 of them
Prevent what?
What type of inhibitors?
Diethylstilbestrol (DES)
Form of ____ with the __ and ___ ___
Two phenolic ___ are set the same ___ as in ____
Why is this important?
Medroxyprogesterone Acetate
In Prempro
Used in combination with?
What is armomatase involved in?
Estrogens indications 4
SAR and the Androstane Nucleus
What is the minimal requirement for activity?
What are the important positions?
Exemestane?
What is it?
Reversible or irreversible?
Tx of?
Nandrolone Decanoate
What is it?
Steroid
Aromatic Subsitution Attenuates Reactivity
Fast Action of N-Alkyl Mustards
And
Slow activation
Which one is better? and Why?
Targeting the Pyrimidine Biosynthetic Pathways
What is required for the production of dTTP
What are the two types of drugs?
Estrogen preparations
What are the key portions for androgenic activity?
What would make it not have androgenic activit?
What portion also exhibits progestin effects?
Mutations that affect normal cell growth can lead to?
Normal cell growth is dependent on 3 things
- Dependent upon ___ and ___
- What leads to new cells?
- What leads to differentiated cells?
Control of Cellular Growth by Various Pathways
- Inhibitors?
- Cell signalling? 2 types
Cancer can Result from Loss of? In 3 kind of way
- Malfunction in what?
- What can lead to transformed cells?
- Damages to? What are tehy called?
Cell–> ____—-> ___
Estrogens natural sources
- Ovaries
- Plcenta
- Adrenal cortex (males and females)
- Plants (flavoniods)
- Mare urine
Clomphene
Employed to promote?
Form?
What SEs?
Blocking 3-keto-4-ene metabolism and 6ahydroxyation
What aspects are improved?
Androgen preparations 3 classes
Finasteride
what does it do?
what does it treat?
Dacarbazine and Temozolomide
MOA?
How are they activated?
Which one would be more selectiv then?
What is a giveaway of what they do?
How is resistance forms?
What is the active toxic componenet?
Methyl diazonium ion
Activation of Dacarbazine via CYP 1A which makes it more selective because id that is overexpressed in the cancer cell it is more/
Temo is acitvated via water
Synthetic Derivatives of Testosterone
What has led to the development of synthetic testosterones?
What are the 2 strats:?
17 ethylyl 19-Norandrostane products
7
Imatinib
Anastrazole and Letrozole Block Oxidative Conversion of Androgens to Estrogens
MOA
Interactions
Other Antimetabolites
Fludarabine, Cladribine, Clofarabine
Gemcitabine
What type of inhibitors are these?
They are all prodrugs
All are what form?
What do halogens do in these drugs?
What does the phosphate prodrug provide?
All of these drugs have one ending?
- All are injectable
- Phosphate provides solubility
- Halogenation slows catabolic processes usually deaminases and phosphorylase can degrade the drug relativeley quickly but with the addition of the halofens on either the base (deaminase) or on the sugar (Phosphorlyase) They can slow this process
What does an ether at the C3 position of an Estrogen cause?
2 things
- Ethers prolong the DOA by preventing sulfation and glucuronidation in vivo
- The ether derivatives are inactive prodrugs that require hepatic dealkylation for activity
Testosterone 4-ene metabolism
what enzyme does it?
What is the product of this? where is this enzyme located?
Flutamide
Where is it absobed ?
What type of metabolism and what does it produce?
what is more potent than this?
Resistance to Cancer Chemo
The R word
- When does it develop?
- What type of cells are more prone to developing resistance?
- They commonly arises from what things? 2
- Current research with agents that disable?
- Why is this complicated and Challenging?
Alkylsulfonates: Busulfan
What forms?
MOA?
- Bifunctional alkylating agent that crosslinks DNA without?
- Has what good leaving group? Similar to CL for what type of rxn
- Insterstrand cross-linking of?
- No activation mean?
- deactivation by?
- Replaced by?
The classical model of APL PAthogenesis
3 points
Pathway from testosterone to androsterone
Intermediates and enzymes needed
Norgestimate
Phenpropionate
what activity? why?
DOA compared to Decanoate?
Promotes?
Antiprogestin: Progesterone Receptor Antagonists
Mifepristine also known as?
What does it do?
How does it do it?
Methotrexate Anion and Cellular Tansport
Glutamate tail
Resistance
Highly crystalline so?
CO2H formulations
Cant cross membrane without active transport
Deprotonated into salts - Formulated for injecttions to improve water solubility
Generalizations about Antihormones
PD
DMPK
Toxicities
What are there SEs related to?
DNA Damage by monofunctional Alkylating Agents
Cause cuts or?
Androgen Antagonists
Toluidides
What are they ?
what doe they do?
what are they used with?
testosterone biotransformation another route
What is the most potent androgen?
how is it formed?
What two modifications at the 17a position do not provide anabolic/androgenic activity?
But one does provide what type of activity?
SAR summary
Feature essential for estrogenic activity 4 points
Modification where can enhance activity?
WHat provides the greatest activity?
Mustards that Attenuated Reactivity
2 of them
Why do these have an imporved therapeutic window? 3 reasons
- Stability how?
- Increased aqeous stability so what? SEs?
- Active in what ways but decrease absorption with?
- Matching
- Multiple myeloma
- chronic lympocytic leukemia, maligant lymphoma and hodgkins
- B-Oxidation to provide phenylacetic acid metabolite
- Proposed that L-Phe actively transported into cells but may enter cells by facilitated diffusion
Camptothecins: Inhibition of DNA Topo?
MOA?
Stability?
Prodrug?
Metabolism?
2 other drugs in this class
Tx of Phytoestrogens?
SERMs
All approved drugs in this category exhibit?
Why have they been given the name SERM?
Other progestins to look at
Estrogens 17b OH esterifications
Provides?
Protects?
What happens in tissue?
Vincristine and Vinblastine
Synthetic Conjugated Estrogens
A and B
Esterified estrogens? Name it
What protects it?
Hydro or lipophilic?
Form?
Duration?
Nandrolone esters
Decanoate and Phenprionate
in general if some thing doesnt have ___ it is more anabolic
What are some features about these esters?
Cholestane skeleton?
Example?
Long side chain and 2 methyl on 13 and 10
18, 19 methyl
Cholesterol
6 carbons
17 α-Ethinyl Estradiol 3-Methyl Ether (Mestranol)
Prodrug or active?
Synthetic lack ___ structure - ?
3 have estrgenic Agonist activity
Estrogenic antagonist activity
3 type then drugs
What is another strategy to prevent the oxidation of the 17b-OH group?
Androgen
SAR for 19-Norandrostane Derivatives
4
Progesterone metabolism due to reduction
what is the product and where are the changes
Medroxyprogesterone Acetate
How is it active?
What types are ective how is this different?
What form provide contraception for 3 months?
Cyclophosphamide and Ifosphamide
Soluble in?
Active in what form?
What is the MOA?
How are these selective?
What is the difference between these two drugs?
What is a product of these drugs that causes toxicity in the bladder?
Certain tumors overexpress P450s so these drugs can be activated within those cells
Bifunction Alkyating Agents: Damage by?
What is the normal way and what is the alkylating agent causing to cause the damage
What are the mechanisms are which these occur?
End results of both?
Labeling alpha or Beta
Oxymetholone
Of the anabolic steroids?
What blocks 17 keto?
Stimulates production of what?
form?
Abiraterone Inhibits the Biosythesis of Testosterone
MOA
What type of molecule?
Blocks CYP17A1 which is responsbile for the coversion of hormones to androgen
Antiandrogens
Metabolic Activation Activation?
MOA
Inhibits the binding of?
Selectivity for receptor
Metabolism and excretion
SEs
Flutamide—> Hydroxyflutamide
- Metabolic activation via CYP1A2 Liver function
- Competitive inhibitor- Inhibits the binding of testosterone and dihydrotestosterone to Androgen receptor–>Causes no translocation of the complex to the nucleus
- More selective to the AR than ER or PR
- Hydrocylated-deacylattion aromatic
- Reversible after stopping the drug:gynecomastia, liver
Nilutamide, Biclutamide
Which one doesnt need activation?
MOA
Stereochemistry
Activation?
AS a class what serious SE do they have?
Biclutamide is sold as a racemate it as a chiral center doesnt need CYP metabolism so safety for patient is better
Norethindrone
What blocks what?
Typically given?
Indications for progestins?
General MOA for N-Mustards which are?
How are they acivated?
How are they deactivated?
Alkylation of DNA by Mechlorethamine
Hydrolysis of 3-sulfates via intestinal _____?
Forms?
Talking about premarin
What is premarin considered?
SAR 17bhydroxyl esterification
Example: testosterone heptanoate
What type of molecule does this end up being?
What is the forM?
Estramustine Phosphate
Actual MOA?
Suitable for?
What type of genic effect?
Purine Antagonists
Amidophosphoribosyl Transferase Inhibitors
How does TPMT Expression vary?
Metabolism Activation via methylation
TPMT leads to an inactive metabolite and thus dose adjustments need to be made it they is high or low expression
Bexarotene Forces?
What does it remove?
What does it promote?
Pentostatin
Its effect is in the what type of pathway? Catabolic or Metabolic
MOA?
4 points
It causes an elevated level of?
Inhibits teh action of what enzyme?
What enzyme does it inhibit?
Catabolic
What binds heme in Anastrozole and Letrozole
Estradiol valerate or estradiol cypionate
Which one is more lipophilic and why?
Cypionate because 17 B SC
Testosterone esters
In general?
Testosterone undecanoate
oral?
Key structural features of RU-486
Antagonism is mediated by?
Semi and Bio synthetic sources of progestins?
Summary of pathway
Where is aromatase involved?
Cell cycle review
G1
G0
S
G2
M
Molecular Mechanisms Of Cancer pathways
Danazol
Contains what type of ring?
Inhibitor of waht?
Suppresses?
form?
what blocks 17 keto
Medroxyprogesterone Acetate (Provera)
What does the liver do? Similar to ___ except for?
What is active?
What decreases reduction of 20-keto
Flutamide
All compounds in this group have what?
3-hydroxyl group on estradiol is subject to ______ metabolism especially with ____ and to a lesser extent with?
What do these things cause?
- Phase II metabolism mostly with sulfation but also with glucuronidation
- Sulfation and Glucuronidation increase polarity and cause more renal elimination
Saw palmetto
17a-Hydroxyprogesterone
Metabolism
what is teh same and what is different in comparison to progesterone metabolism
What does this limit?
A 3-keto like system can mimic the anabolic activity of an androgen drug what modification increases anabolic acitivty over andorgenic activity? What does it look like?
Anthracycline-mediated formation of Free radicals
Role of Aromatase in Cancer?
Block conversion of?
Control?
Aid in?
How are alkylating agents trying to cell the cancer cells?
What can happen with these that should be noted and can cause more issues?
- Continue to expose the cancer cell to promoters that will increase mutations and promote enough that the cell will hopefully die
- These can kill you and be cancerous themselves
Toremifene
Related to?
What reduces its anti-estrogenic potency?
Other SERMs in trials?
Natural Estrogens
Estrone
Activity compared to estradiol?
Vinca Alkaloids: Microtubule?
MOA?
1 and 2
Solubility and Amines?
Methotrexate
MOA
3 things
Alkylating Agents
- Highly reactive molecules that attack? By what mechanism?
- Goal of these?
- Problem?
- Monofunctional?
- Bifunctional?
- Common sites of Mutations? 2
- What phases do these agents act on?
Site of mutation- O6 and N7 positions g bases are generally more prone to alkylate
G1 and S phase where the DNA is the most active
What does estrogen activate? And what does this initiate?
The ER and initiates Transcription
Nat sources of Progestin
4
What is an important note about synthesized progestterone?
Purine Antagonists
MOA 2
They are drug specific
Mercaptopurine and Thioguanine
Incorpotation into DNA inhibiting Chain elongation and promoting apoptosis
Targeting the rate liminitng step of purine biosynthesis, inhibiting formation of what to what?
SAR
What causes anabolic activity in androgens?
How can a drug be resistant to aromatase?
Megesterol Acetate
Active in what form?
Acitivty similar to?
What decreases reduction of 20-keto?
Estradiol
rxn via sulfation and glucuronidation products
Estradiol sulfate and estradiol glucuronidate
All the cholesterol compounds we go over are cis or trans? meaning what?
All trans and its talking about the fusion of the rings
19-Norandrostane
SAR at C17 Improving Progestational over Androgenic acitivty
What group here changes to more progestational?
Ethynyl
3-keto 4 ene testosterone metabolism via?
What is the product?
Antiestrogens
Important
2 classes
Aromatase Inhibitors Block production and
ER Inhibitors - Block the action
Clomiphene
What isomer is the ant antagonist and what one is the agonist?
SAR for 19-Norandrostane Derivatives
Modifications
4 and what do they do
What are the four classes of Antimetabolites?
2 types of Inhibitors in this Area
Where do they interact?
What are they targeting?
Can be?
What phase are they active in
Key progesterone functional groups
What do they do?
Does Testosterone have more anabolic or androgenic acitivty?
Short or fast acting?
Metabolism?
Phytoestrogens?
Picture of what Nucleosides are Doing in the body.
Draw that picture a bunch
Bendamustine:
MOA?
What type of Alkylation?
Antimetabolite: An inhibitor of what?
Metabolism?
This drug compared to Melphanan and Chloramubcil and Mechlorethamine?
Just know that it contains the aromatic portion that give it selectivity and make it better reactive
Similar to Chloram and Melphanan
Fulvestrant and Acolbifene
Norgestrel and Levonorgestrel
Mitotane
Structurally related to?
MOA?
Tox
Antiestrogens
Important in the modification of?
What are the two major groups?
Note on combination of AR blockage and LHRH
CAB
Antihormones
General Featurs
5
- For certain tumors of sex glands and related tissue
- Deprivation of what? Inhibits tumor growth?
- WHy are they used in cocktails?
- Narrow Spectrum compared to?
- Interaction of drug with cytoplasmic receptors require?
Two DES analogs?
How is acrolein detoxified?
What is the rxn that causes this toxicity in the first place?
Mesna is a sacroficial replacement so acrelein doesnt reactive with cysteine from the bladders enzymes
Saw palmetto
Pemetrexed
MOA?
Inhibits the formation of?
So that means no new?
Targets? 3
Transport into cells like how?
Cross resistance?
Gestodene
Cisplatin: Prototypical Platinum Metal Complex
Pt:?
MOA?
- Activation by?
- Forms what? And what does this prevent?
- Some tumors are resistant to?
- Some suggested that what what is not required?
Understanding and Targeting Molecular mechanisms of Cancer
3 Goals of Chemotherapy
- Regulate what processes?
- Requires understanding of?
- Understand the difference between?
Challenges and Problems 3
- Poor understanding of?
- Cancer often involves?
- What type of signalling pathways? What type of cells?
What are the two main progestin products?
New Drugs interfere with Kinase Signaling Pathways
New Addtions
General Properties
Androgens actions and indications
Has two types of activity
and then
19-Norandrostane
SAR
What contribute to the androgenic/anabolic effects?
Readily metabolized to?
what is in the A ring?
Key 19-Andro SAR
Androstane Nucleus without?
Ethinyl estradiol
What is it?
Prodrug or active?
Important to note about the 17a?
What is it used as?
Other inhibitors of thymidine biosynthesis
2
Which on requires less activation?
How do they overcome resistance?
Retinoids
Structurally related to?
What factors?
Bexarotene ?
Estrogens aromatic where?
A rings
Megestrol Acetate
MOA
SEs
Signaling Cascade Inhibitors: Kinase Inhibitors
Conjugated Estrogens
Premarin
Saturation in the B ring?
What is important to note about the mixture?
Isolated from?
What form?
Sodium Estrone Sulfate
Conjugated estrogens have grreater water solubility- this is the form found in urine
PO, IM, IV
5-F-dUMP Irreversibly and Covalently Modifies TS
Cell dies due to?
Exemestane
Structurally related to?
MOA?
Double bond?
Michael Acceptor
DOuble bond add extra binding covalent binding with aromatase
Cholesterol —>? Preg?
What is involved?
Nandrolone Decanoate
What is it?
Steroid
Aromatase Inhibitors
Letrozoel and Anastrazole
ADME
SEs due to?
Abiraterone
MOA
Resistance
Interaction of Cisplatin With DNA
Resistance?
Common sites of Binding?
Mutations to the Polymerases that can pass the blockage
Adjacent G-G and G-A
Progesterone: Metabolism to?
What is added and different?
What does it get metabolized by?
Addition at 6 you should know whay its metabolized to
