GMS 6504 Exam Questions and Answers 100- Correct!!

GMS 6504 Exam Questions and Answers
100% Correct!!

Lipinski's |rule |of |5 |- |ANSWER-- |Poor |absorption |or |permeation |are |more |likely |when:
1. |mass |greater |than |500 |Da
2. |highly |lipophilic |- |logP |> |5
3. |more |than |5 |hydrogen |bond |donors
4. |more |than |10 |hydrogen |bond |acceptors

Partition |coefficient |- |ANSWER-p |= |C(octanol)/C(water)
- |ratio |of |the |equilibrium |concentrations |of |dissolved |substance |in |a |two-phase |system
|containing |two |largely |immiscible |solvents |(water |& |octanol)

- |Log10(P)

Improved |Lipinski |Parameters |- |ANSWER-1. |Partition |coefficient |Log(P) |-0.4-5.6 |range
2. |Molar |refractivity |from |40-130
3. |Molecular |weight |from |160-500
4. |Number |of |atoms |from |20-70
5. |Polar |surface |area |no |greater |than |140 |A^2

CNS |Drugs |- |ANSWER-- |need |lower |Polar |Surface |Area |(A^2) |to |cross |BBB

Modification |of |Proteins |and/or |nucleic |acids |- |ANSWER-- |bad |if |unanticipated |& |non-
selective
- |good |if |selective

Esters, |amide |bonds, |& |disulfide |bonds |- |ANSWER-- |labile |in |biological |systems
- |esters |most |labile
- |useful |for |creating |pro-drugs |but |can |be |broken |down |in-vivo

Esters |- |ANSWER-- |most |commonly |bound |pro-drug |incorporate
- |body |is |full |of |esterases |capable |of |breaking |down |into |active |form

Easily |druggable |targets |- |ANSWER-- |enzymes |- |kinases, |phosphatases, |histone
|deacetylases

- |cell |surface |receptors |- |GPCRs, |RTKs, |cytokine |receptors

Undruggable |targets |- |ANSWER-- |transcription |factors
- |scaffolding |proteins
- |protein-protein |interactions |involving |large, |flat |protein-protein |interfaces

, Undruggable |approaches |- |ANSWER-- |higher |order |complex |formation |(rapamycin,
|FK506, |cyclosporine) |- |chemobodies

- |Synthetic |lethality
- |RNAi/Antisense |RNA
- |genome |editing |(CRISPR)
- |SAR |by |NMR

ATP |inhibitors |- |ANSWER-- |ATP-competitive |inhibitors |are |easy |to |design
- |kinases |are |present |in |nearly |all |signalling |pathways

- |ATP |kinase |binding |sites |are |evolutionarily |conserved
- |high |functional |redundancy |among |kinases

Gatekeeper |- |ANSWER-- |defines |size |of |specificity |pocket
- |bigger |the |keeper |smaller |the |size |of |the |specificity |pocket

Specificity |pocket |- |ANSWER-- |varies |in |size |amonnst |different |ATP |sites

Gatekeeper |makeup |- |ANSWER-- |predomenently |methionine, |threonine, |luecine, |or
|phenylanalnine




ATP-competitive |kinse |inhibitors |- |ANSWER-- |recognize |the |active |conformation |of
|kinase |(type |1)




Irreversible |kinase |inhibitors |- |ANSWER-- |covalently |react |with |cysteine |residues |within
|the |kinase |near |the |atp |binding |site




Kd |- |ANSWER-- |dissociation |constant
- |concentration |of |a |ligand |where |half |of |the |binding |sites |on |a |protein |are |bound
- |circle |size |is |proportional |to |binding |affinity

Difficult |to |develop |specific |active |site |kinase |inhibitors |- |ANSWER-- |due |to |gatekeeper
|mutations

- |active |site |mutations
- |resistance |over |time
- |overexpression |of |kinase
- |functional |redundancy

William |Coley |- |ANSWER-- |father |of |cancer |immunotherapy
- |developed |concoction |mixture |of |killed |bacteria |that |was |injected |intratumorally, |causing
|cancer |regression

- |results |were |hard |to |duplicate |due |to |Coley's |poor |record |taking |skills

Cross-presentation |of |tumor |antigens |- |ANSWER-- |APCs |pick |up |tumor |antigens |and
|present |to |dendritic |cells