QUESTIONS WITH SOLUTIONS GRADED A+
◍ What are the three types of Displacement Binding antagonists?.
Answer: competitivenoncompetitiveallosteric
◍ What kinds of functional groups are used most commonly to make
pro-drugs?.
Answer: depends on the functional group the drug posseses (don't need to
know specifics)biologically labile functional groups
◍ What is the Specific Binding equation?.
Answer: the drug that is bound to the receptor that we are targetingmeasured
with Langmuir equation[A] / [A] + Kdgives proportion of specific binding
achieved with a particular concentration of agonist
◍ What is the overall basic reaction catalyzes by kinases?.
Answer: protein + ATP --> Phosphorylated-protein + ADP
◍ How are Allosteric Modulators used as a co-therapy?.
Answer: antibodies bind at lower concentrations so less can be usedthis is
good because they are expensive
◍ What is Cygwin and what is it used for in molecular docking?.
Answer: the Doc program is a linux programso this is a linux emulator that
can be used on windows computers
◍ What are the different types of tumor antigens?.
Answer: 1. Normal cell displaying self-antigens = No T cell response2.
Mutated self protein that does not contribute to tumorigenesis3. Product of
oncogene or mutated tumor suppressor gene4. Overexpressed or aberrantly
expressed self protein5. Oncogenic virus
◍ What type of molecule does a Michael acceptor typically react with in the
, body?.
Answer: cysteine
◍ Describe the "P loop" of a kinase.
Answer: between ß1 and ß2close to the phosphate group and involved in
binding phosphate of ATPGXGXXG sequence (x is just another AA)
glycines allow for close approach of the triphosphate of the ATP
◍ Describe the selectivity of Tykerb/Lapatinib.
Answer: treats breast cancervery selective drug, typically only inhibits
HER2 and EGFR kinasesselective because it binds ATP binding pocket and
allosteric site
◍ What are the good points to using kinases as therapeutic targets?.
Answer: ATP-competitive inhibitors are easy to designkinases are involved
in just about every signaling pathway
◍ What are some things we can decide to measure?.
Answer: 1. receptor translocation2. interaction with cytosolic proteins3.
second messenger production4. gene expression5. cellular response
◍ What is a NAM-agonist?.
Answer: NAM that also produces some response on its own
◍ Why would we want an efficacy-driven agonist?.
Answer: when number of receptors are reduced 100% occupancy can still be
achieved by increasing drug amountwe can use this in disease states
involving downregulation of receptorsex. insulin receptor in diabetes
◍ What are system dependent parameters in determining response in a test
system?.
Answer: 1. number of receptors2. cellular machinery = signal cascades to
achieve desired effect3. presence of other drugs (and are they competitive or
noncompetitive)(most things are dependent on the system and have an
effect, only system independent parameters don't)
◍ How are cysteine residues used to increase specificity of a kinase inhibitor?.
, Answer: by converting it from a reversible to an irreversible
inhibitorirreversible kinase inhibitors covalently react with cysteine residues
within the kinase near the ATP binding siteif you know how a molecule is
going to bind in the ATP pocket, you can add a thiol reactive group to react
with a cysteine and convert it into a covalent inhibitor, making apparent
affinity higher (irreversible)
◍ What is Occupancy Theory?.
Answer: response is proportional to fraction of receptors that are
occupiedi.e. 100% response is obtained when all receptors have ligand
bound
◍ Who is William Coley?.
Answer: the father of cancer immunotherapyin 1891 he injected "Coley's
toxin" a mixture of killed bacteria and intratumorally, observed tumor
regressionbut his study did not follow good scientific protocols with bad
reproducibility and fell out of favor
◍ When do you use the peak area and when do you use peak height for
measurements of concentration?.
Answer: for precision use peak areafor accuracy use peak height
◍ Describe Gemtuzumab Ozogamicin (Mylotarg).
Answer: Anti-CD33 humanized monoclonal antibody conjugated to
calicheamicin anti-tumor antibiotic that causes DNA strand scissionuses in
relapsed/refractory CD33-positive AML as a monotherapy or with chemo
◍ Define Immunotherapy.
Answer: treatment of disease by inducing, enhancing, or suppressing an
immune response
◍ Why do we do Displacement Binding experiments?.
Answer: radioactive ligands are expensive to makepossession of radioactive
material is limitedallows use of one radioligand and a series of cold ligands
◍ What is Signal Amplification?.
Answer: multiplying different functions together to achieve a greater
, response
◍ What do Gs or Gq protein do to melanin.
Answer: causes dispersion so appears dark
◍ What are some cons of Functional Assays?.
Answer: amplified signalscan potentially mask important information
◍ Describe the cancer-immunity cycle.
Answer: 1. Release of cancer cell antigens (from cell death)2. Cancer
antigen presentation on dendritic cells and APCs3. Priming and activation
with APCs and T cells4. Trafficking of T cells to tumors (CTLs)5.
Infiltration of T cells into tumors (CTLs, endothelial cells)6. Recognition of
cancer cells by T cells (CTLs, cancer cells)7. Killing of cancer cells
(immune and cancer cells)REPEAT
◍ What are the 4 pharmacological test systems?.
Answer: 1. Animal receptors = animal tissues2. Human receptors =
surrogate cells like a cell culture3. Human receptors = human target cells4.
Human receptors = human target cells under the influence of pathology
◍ ~10% increase in fraction of organic solvent in water causes.
Answer: a 2-3x decrease in binding
◍ Describe High-dose recombinant interleukin-2.
Answer: for metastatic renal cell carcinoma (mRCC) and metastatic
melanoma (mM)promotes the differentiation of T cells into effector T cells
and memory T cells in the presence of antigenproblems include promotion
of Tregs, which could be lethal
◍ Describe Column Chromatography.
Answer: a glass tube with a solid inside (Stationary phase), then filled with
liquid (mobile phase)solution is added and gravity pulls everything downas
solution passes stationary phase the sample separates into those that prefer
the solid or liquid
◍ Describe the general structure of some ATP-competitive kinase inhibitors.