cancer therapeutics 3

type 1 kinase inhibition conformation

C helix in

DFG in

type 3 kinase inhibition conformation

C helix out

DFG in

SSB DNA repair mechanism

PARP

DSB DNA repair mechanism

homologous recombination

synthetic lethality

cell death as a result of using PARP inhibitors

angiogenesis

process of formation of new blood vessels

pro-apoptotic effecters

Bax Bak

apoptosis sensitizers

BH3 family

pro-survival protein

BCL-2

gene translocations that may lead to tumorigenesis

BCR-ABL

EML4-ALK

erlotinib target

EGFR

neratinib target

pan-HER

therapeutic approaches to target HER receptors

TK inhibitors

monoclonal antibodies

ADCs

thereapeutic approaches to interfere with angiogenesis

monoclonal antibodies against VEGF

monoclonal antibodies against VEGFR

anti-VEGFR kinase inhibitors

how pertuzumab and trastuzumab are similar

both are human mabs against the HER2 receptor

pertuzumab and trastuzumab bind to

different domains on HER2

rationale for using BRAF and MEK inhibitors together

slow down emergence of resistance and lower risk of some AEs

entrectinib MoA

NTRK inhibitor

crizotinib MoA

ALK inhibitor

venetoclax mimics

BH3

agents that cause acneiform rashes and PRIDE syndrome

EGFR inhibitors

agent that may cause cardiomyopathy

trastuzumab

agents associated with HFSR

sorafenib and dabrafenib

why does combining dabfrafenib with a MEK inhibitor reduce HFSR

keratine production is due to MAP activation, which is increased by BRAF inhibition

agent that causes anemia

olaparib

agents that may cause QT prolongation

entrectinib

sorafenib

adagrasib

ribociclib

osimertinib

crizotinib

class that causes hypertension, thromboembolism, GI perforation, and impaired wound healing

VEGF pathway inhibitors

class of agents that may cause myelosuppression, maculopapular rashes, fluid retention, and edema

BCR-ABL inhibitors

agent that may cause CNS effects

entrectinib

mechanism of resistance to erlotinib

T790M mutation

agent used in T790M mutation

osimertinib

BRAF mutation where dabrafenib is effective

V600E

interaction that brings the C helix in

salt bridge

mechanism of resistance to nilotinib

T315I mutation

amino acid in KRAS mutation that sotorasib binds to

cysteine in G12C

ABL conformation that allows for binding of imatinib

inactive

highly selective inhibitor to BCR-ABL

asciminib

asciminib binding site

myristic acid binding site

agents used in CML

BCR-ABL inhibitors

agents used in CLL

venetoclax

H bonding in erlotinib

basic nitrogen to hinge residue

neratinib feature that binds to the allosteric site

bottom pyridine ring

general feature in kinase inhibitors that binds to adenine pocket

quinoline ring

group in imatinib that provides allosteric binding

piperazinyl ring

group in imatinib that interacts with Thr315

nitrogens in the anilino pyrimidine ring

structural feature in ponatinib that binds to BCR-ABL with gatekeeper mutation

alkyne group

structural feature that leads to covalent binding in sotorasib

alpha, beta-unsaturated ketone

olaparib contains which moiety that competes with a biomolecule in PARP

nicotinamide competes with NAD+

venetoclax mimics this structure

alpha helix

agent administered with aromatase inhibitors in ER+ breast cancer

palbociclib

palbociclib MoA

CDK4/6 inhibitor prevents RB phosphorylation

T315I is a

gatekeeper mutation

agent used in cancers developing T315I mutation

ponatinib or asciminib

many kinase inhibitors are non specific because

they target the ATP binding site

cetuximab is not used in mutant RAS tumors because

it inhibits a step upstream of the mutation

agent that inhibits its target via a protein protein interaction

venetoclax

bevacizumab target

VEGF

ramucirumab target

VEFGR2

type 1.5 inhibitors

dabrafenib

lapatanib

type 3 kinase inhibitor

trametinib

which HER does not have an endogenous ligand

HER2

which HER is not a tyrosine kinase

HER3

erlotinib inhibition is

reversible

trastuzumab is eliminated by

internalization

afatinib, sotorasib, and osmertinib bind

cysteine