Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PHRM 864 > L5-6 Kinases > Flashcards

L5-6 Kinases Flashcards

1
Q

what do all of the kinase inhibitors bind to?

A

the ATP-binding site of protein kinases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what AA is a common target of several kinases? (slide 19)

A

tyrosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what 3 AAs can be phosphorylated and are substrates for kinases and why

A

Tyrosine
Serine
Threonine
they all have -OH group

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what balances the activity of kinases by removing phosphates?

A

phosphatases - lol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what common step in cell signaling activates kinase activity?

A

dimerization of something somewhere idk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Types of kinase inhibitors:
Bind to active conformation of the kinase
A. Type I
B. Type II
C. Type III

A

A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Types of kinase inhibitors:
Bind and stabilize the inactive conformation of the kinase
A. Type I
B. Type II
C. Type III

A

B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Types of kinase inhibitors:
Occupy an allosteric pocket outside of the ATP-binding pocket
A. Type I
B. Type II
C. Type III

A

C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Competitive Inhibitors bind kinase in a ________ fashion and therefore must compete with _______ for binding.

A

reversible
ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What type of TKI is gefitinib?

A

Type I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

where does gefitinib bind?

A

The ATP-binding site of the TK domain of EGFR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

EGFR functions through what?

A

TK activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

EGFR signaling induces what?

A

cell proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Erlotinib is a small molecule ________ inhibitor of EGFR tyrosine kinase

A

Reversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

T or F:
Erlotinib is a competitive inhibitor

A

True, inhibits the enzyme by binding to the ATP binding site in the kinase domain (of EGFR)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Inhibition of kinase activity turns off what?

A

the signal to proliferate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Gefitinib and Erlotinib are both approved for patients that fall under what criteria?

A

NSCLC
EGFR exon 19 or 21 mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

3 common adverse effects of gefitinib and erlotinib

A

fatigue
rash
diarrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Afatinib is a ______ inhibitor of all ____ receptors

A

covalent**
ErbB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is Afatinib approved for?

A

EGFR mutant NSCLC with EGFR mutations (exon 19 and 21)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is dacomitinib approved for?

A

non-resistant EGFR mutant lung cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is the main side effect “we should know” from EGFR inhibitors?

A

skin rash

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what mutation causes resistance to gefitinib?

A

T790M **

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Osimertinib:
- A ___ generation EGFR inhibitor
- ______ kinase inhibitor
- Effective against the ____ mutant EGFR

A

third
covalent
T790M

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
EGFR forms a heterodimer with ______
HER2 (ErbB2)
25
HER2 is genomically _____ in breast cancer
amplified
26
Lapatinib: - small molecule TKI that blocks _____ and _____ signaling
HER2 EGFR
27
Lapatinib: - selective for the treatment of _______ breast cancer
HER2+.
28
lapatinib: - currently approved (in combination with capecitabine) for the treatment of ________ ________ breast cancer in pts who have progressed on other therapies
advanced metastatic (late stages)
29
T or F: Lapatinib is an irreversible inhibitor of both EGFR and HER2
false, reversible
30
3 common side effects of lapatinib
diarrhea nausea vomiting (also watch for sxs of congestive heart failure for some reason)
31
Tucatinib: - small molecule TKI that preferentially binds ____
HER2
32
Tucatinib: - selective for the tx of _______ ______
HER2+ breast cancer
33
lapatinib: - currently approved (in combination with capecitabine and trastuzumab) for the treatment of ________ ________ breast cancer in pts who have progressed on other therapies
advanced metastatic (sorry same card twice kinda minus the trast drug)
34
Tucatinib has reduced adverse reactions compared to lapatinib, why is this?
since it is more selective for HER2
35
Which compounds inhibit EGFR? A. Gefitinib B. Osmertinib C. Afatinib D. Lapatinib E. All of the above
E
36
What mutation in EGFR confers resistance to 1st and 2nd generation EGFR inhibitors? A. L858R B. Exon 19 deletion C. Exon 14 deletion D. T790M
D
37
what the fuck is the FLT3 (fms-like tyrosine kinase 3) ligand?
a cytokine receptor important for hematopoietic cell survival and proliferation
38
FLT3 mutations are found in 30% of what?
acute myeloid leukemia (AML)
39
Mutations in FLT3 lead to increased ______ and decreased______
proliferation apoptosis
40
1st gen FLT3 inhibitors (midostaurin) are broad ________ _______
kinase inhibitors, no wonder theyre in this deck huh
41
2nd gen FLT3 inhibitors (crenolanib) are better than 1st gen, but why?
more specific
42
Type II inhibitors (FLT3 specific) (e.g. Quizartinib) are specific for what? *
ITD (internal tandem duplication) mutations
43
MET is the receptor for what?
hepatocyte growth factor (HGF)
44
capmatinib is a _____ inhibitor
MET (my friend wears a METS baseball CAP?)
45
In addition to directly driving tumor cell growth, Vascular Endothelial Growth Factor Receptor (VEGFR) is also critical to __________ __________making it an attractive target.
tumor angiogenesis
46
if you see "Bcr-Abl" what should you instantly think about?
philadelphia
47
Bcr-Abl: _______ protein with TK activity
fusion
48
Philadelphia chromosome (Ph1) is the prototype ___________ ____________
chromosomal translocation
49
The Ph1 chromosome is demonstrable in ~95% of what type of cancer
chronic myeloid leukemia (CML)
50
T or F: Bcr-Abl is a chimeric protein
true i guess idk
51
T or F: Bcr-Abl is a crucial protein for apoptosis
False, it actually drives several proliferation pathways
52
if you see Bcr-Abl, what type of cancer should you think of?
CML
53
T or F: Bcr-Abl acts as an overexpressed kinase
True (i think the Abl part is a TK)
54
The kinase activity of the Bcr-Abl protein is _________ active. What does this mean?
Constitutively constitutive activity results in malignancy **
55
Imatinib is a Type ____ small molecule inhibitor of the Abl TK
Type II
56
what does inhibiting the Abl TK result in? (2 things)
reduced proliferation and enhanced apoptosis in CML and GIST
57
Imatinib primary indication
Treatment of CML (IM A CHRONIC nib?)
58
toxicities of imatinib
N/V edema neutropenia and thrombocytopenia
59
so basically, if an exam question says anything about CML whats your next move?
clicking the shit that says Imatinib
60
Ponatinib inhibits what?
Bcr-Abl, so both components instead of just the one?
61
T or F: Ponatinib is effective against ALL the major mutant forms of Bcr-Abl
True, actually
62
Ponatinib can inhibit the "gatekeeper" ** mutation ______ that is resistant to all other Bcr-Abl compounds
T315
63
okay here's the scene. you're sitting in the exam room. you click to question 33. It says something about T315. What do you do?
SMACK whatever option has Ponatinib
64
EML4-ALK translocation is significant driver event in what?
lung cancer
65
what is the ALK part of EML4-ALK?
something about wild type ALK. he is a transmembrane receptor TK similar to EGFR
66
is EGFR a receptor tyrosine kinase (RTK) ?
yes
67
When ALK becomes "inappropriately" fused with ELM4, what happens?
it becomes cytoplasmic and constitutively active (which is bad im pretty sure)
68
What is the significance of ALK becoming cytoplasmic after fusing to ELM4?
it turns on pathways that ALK would not normally turn on
69
Alectinib MOA-ish
more specific inhibitor of ALK
70
T or F: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase
True
71
T or F: Alectinib requires a companion diagnostic test for the fusion gene
true
72
Indication of Alectinib
ALK+ NSCLC who have progressed on or are intolerant to crizotinib
73
what other drug is an ALK inhibitor that isnt alectinib
Brigatinib
74
when you see BRAF what cancer do you think of?
boobie
75
Dabrafenib MOA
2nd gen BRAF-V600 inhibitor
76
Dabrafenib approved in combo with _______ for tx of BRAF V600E/K-mutant metastatic melanoma
trametinib (I MET this guy and he DABbed me up)
77
Valine(V) 600E/K is a mutation you see in what? what drug do you use when you see it?
melanoma Dabrafenib
78
Trametinib inhibits the kinase activity of ____ and _____
MEK1 and MEK2
79
Trametinib has a limitation of use, what is it?
pts who have received prior BRAF inhibitor therapy
80
3 most common AE's for trametinib
Rash* diarrhea lymphedema.
81
Which type of inhibitor is Trametinib? A. 1st gen (active site) B. 2nd gen C. 3rd gen (allosteric site)
C. allosteric
82
Encorafenib and Binimetinib (very niche on slide 59) can both be used in combo for pts with what?
UNRESECTABLE or metastatic melanoma with a BRAF V600E. or V600K mutation
83
Brutons TK (BTK) is important for normal __ cell activity and __ cell tumor growth
B and B
84
Ibrutinib is a covalent inhibitor of ?
BTK (brutons TK) (woah brut is in the name!)
85
BTK is commonly associated with what?
sorry this is vague but its B-cell malignancies
86
BTK inhibitors are used primarily in which 2 cancers
mantle cell lymphoma (MCL) chronic lymphocytic leukemia (CLL)
87
2nd gen BTK inhibitor: A. Ibrutinib B. Acalabrutinib
B
88
T or F: Both ibrutinib and acalabrutinib are covalent BTK inhibitors
True
89
what is acalabrutinib indicated for?
B-cell lymphoma (MCL and CLL) just like ibrutinib
90
Acalabrutinib also targets what niche thing?
Cys481
91
what is rapamycin more commonly known as?
Sirolimus
92
what do the rapamycin analogs (sirolimus) inhibit?
the fxn of mTOR
93
wtf is mTOR
a serine-threonine kinase
94
T or F: Everolimus inhibits both mTORC1 mTORC2
False, it only inhibits mTORC1
95
Everolimus has a second therapeutic use that isnt for oncology reasons, what is it?
organ transplants
96
T or F: Targeted therapies (kinase inhibitors) avoid many toxicities that other products can cause
true
97
what kind of DNA is used from lung cancer biopsies to determine drug therapy
GENOMIC
98
Oncotype Dx helps to predict ________ and therefore can prevent overtreatment, but these tests (do/do not) drive indications for specific therapies
recurrence do not

PHRM 864 (29 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions