Exam (elaborations)
GMS 6504 EXAM WITH VERIFIED ANSWERS
- Course
- Institution
GMS 6504 EXAM WITH VERIFIED ANSWERS
[Show more]
Content preview
GMS 6504 EXAM WITH VERIFIED ANSWERS1. Lipinski's rule of 5: - 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
| | | | |
2. Partition coefficient: 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)
3. Improved Lipinski Parameters: 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
| | | | | | |
4. CNS Drugs: - need lower Polar Surface Area (A^2) to cross BBB
| | | | | | | | | | |
5. Modification of Proteins and/or nucleic acids: - bad if unanticipated & non-se- | | | | | | | | | | |
lective
|
- good if selective | |
6. Esters, amide bonds, & disulfide bonds: - labile in biological systems
| | | | | | | | | |
- esters most labile | |
- useful for creating pro-drugs but can be broken down in-vivo
| | | | | | | | |
7. Esters: - most commonly bound pro-drug incorporate | | | | | |
- body is full of esterases capable of breaking down into active form
| | | | | | | | | | |
8. Easily druggable targets: - enzymes - kinases, phosphatases, histone deacety-
| | | | | | | | |
lases
|
- cell surface receptors - GPCRs, RTKs, cytokine receptors
| | | | | | |
9. Undruggable targets: - transcription factors | | | |
- scaffolding proteins |
- protein-protein interactions involving large, flat protein-protein interfaces | | | | | |
10. Undruggable approaches: - higher order complex formation (rapamycin, | | | | | | |
FK506, cyclosporine) - chemobodies
| | | |
- Synthetic lethality |
- RNAi/Antisense RNA |
- genome editing (CRISPR) | |
- SAR by NMR | |
11. ATP inhibitors: - ATP-competitive inhibitors are easy to design
| | | | | | | |
- kinases are present in nearly all signalling pathways
| | | | | | |
1 |/ |11
, - ATP kinase binding sites are evolutionarily conserved
| | | | | |
- high functional redundancy among kinases
| | | |
12. Gatekeeper: - defines size of specificity pocket | | | | | |
- bigger the keeper smaller the size of the specificity pocket
| | | | | | | | |
13. Specificity pocket: - varies in size amonnst different ATP sites | | | | | | | | |
14. Gatekeeper makeup: - predomenently methionine, threonine, luecine, or | | | | | | |
phenylanalnine
|
15. ATP-competitive kinse inhibitors: - recognize the active conformation of ki- | | | | | | | | |
nase (type 1)
| | |
16. Irreversible kinase inhibitors: - covalently react with cysteine residues within | | | | | | | | |
the kinase near the atp binding site
| | | | | | |
17. Kd: - dissociation constant | | |
- concentration of a ligand where half of the binding sites on a protein are bound | | | | | | | | | | | | | |
- circle size is proportional to binding affinity
| | | | | |
18. Difficult to develop specific active site kinase inhibitors: - due to gatekeeper| | | | | | | | | | |
mutations
|
- active site mutations | |
- resistance over time | |
- overexpression of kinase | |
- functional redundancy |
19. William Coley: - 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
| | | | | | | | | | |
20. Cross-presentation of tumor antigens: - APCs pick up tumor antigens and | | | | | | | | | |
present to dendritic cells
| | | |
- dendritic cells present tumor antigens and co-stimulators to CD8+ cells and induce
| | | | | | | | | | |
tumor-targeted execution
| |
21. Bone marrow transplant: - form of cancer immunotherapy | | | | | | |
- chemo kills existing bone marrow which is replaced with donor marrow
| | | | | | | | | |
- strive for graft vs. tumor effect
| | | | |
- graft vs. host disease is a complication
| | | | | |
22. -o-: - mouse | |
23. -xi-: - chimeric | |
- 75% human & 25% murine (mouse)
| | | | |
24. -u-: - human | |
25. -xizu-: - chimeric/humanized | |
26. -zu-: - humanized | |
- 95% human & 5% murine (mouse)
| | | | |
2 |/ |11
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller Fordenken. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $15.49. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
82871 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy study notes for 14 years now