Medchem

Question 1

Bevacizumab

Answer 1

Targets VEGF and can be used to prevent angiogenesis
Selectively binds VEGF and can stop it from binding to its receptors, reducing microvascular growth of tumour blood vessels and limiting blood supply to tumours
Neutralises VEGFA

Question 2

Afilbercept

Answer 2

Human recombinant fusion protein with antiangiogenic effects - functions as a decoy receptor to bind to VEGF
Reduces production of VEGF

Question 3

Ramucirumab

Answer 3

Binds VEGFRs, inhibiting angiogenesis pathways

Question 4

Ipilimumab

Answer 4

Anti-cancer antibody that targets CTLA-4
Results in T-cell proliferation and cytokine release, resulting in an amplified immune response

Question 5

Pembrolizumab

Answer 5

Binds to PD-1 on the surface of activated T-cells, blocking its binding by ligands, which results in the activation of T-cell-mediated immune responses against tumor cells.

Question 6

Nivolumab

Answer 6

Binds to PD-1 on the surface of activated T-cells, blocking its binding by ligands, which results in the activation of T-cell-mediated immune responses against tumor cells.

Question 7

Durvalumab

Answer 7

New PDL-1 inhibitor. Binding results in the release the inhibition of immune responses, without inducing antibody-dependent cell-mediated cytotoxicity.

Question 8

Herceptin

Answer 8

EGFR inhibitor. Prevents HER2-mediated signalling

Question 9

Cetuximab

Answer 9

Inhibits growth and survival of EGFR-positive tumours. It promotes antibody-dependent cellular cytotoxicity (ADCC) against certain human tumour types

Question 10

Sorafenib

Answer 10

Has multi-kinase inhibitory action. Inhibits the RAF/MEK/ERK pathway and reduces angiogenesis by inhibiting EGFR.

Question 11

Dasatinib

Answer 11

Blocks the ATP binding site of Src

Question 12

Sotorasib

Answer 12

Binds to the cys residue in mutated Ras, locking it in its inactive form.

Question 13

Gefitinib (Iressa)

Answer 13

First gen. EGFR inhibitor

Question 14

Erlotinib

Answer 14

First gen. EGFR inhibitor

Question 15

Lapatinib

Answer 15

2nd gen. EGFR inhibitor

Question 16

Afatinib

Answer 16

2nd gen EGFR inhibitor

Question 17

Rocilentinib

Answer 17

3rd gen EGFR inhibitor, can target T790M mutation

Question 18

Osimertinib

Answer 18

3rd gen EGFR inhibitor, can target T790M mutation

Question 19

Advexin

Answer 19

Adenovirus that delivers normal P53 to the cells, outcompeting mutated P53

Question 20

Pifithrin

Answer 20

Suppresses normal P53 in normal tissue, reducing the effects of chemo

Question 21

PRIMA-1

Answer 21

suppresses mutant P53 expression

Question 22

Imatinib (Glivec)

Answer 22

Targets BCR-Abl translocation, by inhibiting Abl tyrosine kinase

Question 23

Idasanutlin (AR)

Answer 23

MDM2 inhibitor, preventing MDM2 from inhibiting P53

Question 24

TERT-vaccines

Answer 24

Stimulate the immune system to target cells expressing TERT, the gene encoding telomerase, that maintains the length of telomeres, and is thus found in cancer cells.

Question 25

Methotrexate

Answer 25

Dihydrofolate analogue, binds to DHFR. Folate antagonist

Question 26

5-FU

Answer 26

Pyrimidine antagonist fluorine atom ends up on dUMP (fdUMP), which binds to TS and 5,10-CH2-T to form a ternary complex the F atom is too electronegative for the complex to break apart, so TS is trapped and the folate cycle cannot continue

Question 27

6-MP

Answer 27

Purine antagonist It is converted into an active metabolite (by HGPRT?), thio-IMP, which is further metabolised into thio-GMP and thio-dGTP, which are incorporated into DNA, resulting in impaired DNA replication.

Question 28

Gemcitabine

Answer 28

Sugar modified nucleoside Gemcitabine (F2dC) is readily converted into triphosphate F2dCTP This inhibits DNA polymerases as an analogue of dCTP F2dC --> (dCk) F2dCMP --> (UMP kinase) F2dCDP --> (NDP kinase) F2CTP depletion of dCTP as a result of F2dCDP results in activation of dCk. Activation of dCk increases formation of F2dCMP (self-potentiation of Gemcitabine)

Question 29

Cytarabine

Answer 29

Inhibits DNA polymerases as an analogue of dCTP

Question 30

Taxane ligands - Paclitaxel

Answer 30

MSA. Binds near the ML surface on the B-subunit, on the inside of the MT Fits between small gaps and induces a conformational change, disrupting MT dynamics

Question 31

Vinca alkaloids

Answer 31

MDA Binding site is at the +end surface of B-tubulin - forms a wedge, interfering with the incorporation of new heterodimers +end remains curved and MT wall cannot form

Question 32

Colchicine

Answer 32

binding site is located between the alpha and beta subunits binding stabilises the heterodimer in the curved formation binds to soluble pool and is incorporated destabilises MT at high concentrations

Question 33

Carfilzomib (AR)

Answer 33

Proteasomal inhibitor could attenuate paclitaxel resistance through activation of hypoxia-inducible factor 1

Question 34

Nitrogen mustards

Answer 34

Alkylator Target guanine N7 and exo-cyclic NH2, as well as Adenine N7 and N3 Chlorine atoms are lost, and the DNA becomes covalently bound to the drug

Question 35

Estramustine

Answer 35

Alkylator A nitrogen mustard tagged with an oestrogen molecule, used to target oestrogen-dependent cells. Can also be used in prostate cancer because the estradiol slows the body's testosterone production, which the prostate cancer needs to grow

Question 36

Temozolomide

Answer 36

Alkylator (DNA methylator) Transporter of a methyldiazonium ion, which is attaches to the DNA and methylates it. T is broken down by water hydrolysis in order to release the methyldiazonium ion.

Question 37

CPIs (Adozelesin, Bizelesin)

Answer 37

DNA minor groove binder (covalent) - anti-tumour antibiotics Their stereochemistry in the isopropyl ring is essential, as only one isomer is reactive Bizelesin forms inter-strand DNA duplex crosslinks, while Adozelesin forms mono-alkylation duplex adducts

Question 38

PBDs

Answer 38

DNA minor groove binder (covalent) - anti tumour antibiotics Form a reversible amime bond between the eco-cyclic NH2 of guanine and the C2 position on the PBD

Question 39

Distamycin and Netropsin

Answer 39

DNA minor-groove binders (non-covalent)

Question 40

Mitomycin C

Answer 40

DNA minor-groove binder (covalent) Reduction of the molecule occurs, releasing a molecule of methanol - the now-reduced mitocene interacts with the DNA DNA alpha attack occurs, and a second molecule of DNA then reacts with the drug. 2 tags on DNA formed HYPOXIA-selective drug

Question 41

Patrin/O-6-benzylguanine

Answer 41

MGMT inhibitors - pseudosubstrates that deplete MGMT levels, which normally removes adducts from alkylators Can therefore be used in combination with Temozolomide to treat high grade glioma

Question 42

Olaparib

Answer 42

Inhibits PARP1, 2 and 3 Binds to active site of PARP and prevents it from carrying out its function

Question 43

Rucaparib

Answer 43

Inhibits PARP1 and 2 Binds to the active site of PARP and preventing it from carrying out its function

Question 44

Nitromidazole

Answer 44

Has radiosensitising properties so can be used in hypoxic tumours Reduces glutathione concentration and inhibits glutathione S-transferase This causes tumours to become more sensitive to ionising radiation A pro-drug that is activated by low oxygen levels

Question 45

Imetelstat (AR)

Answer 45

Inhibits telomerase activity A synthetic oligonucleotide that targets the RNA component of telomerase Promising against NSCLC, but need more trials

Question 46

Bleomycin

Answer 46

Cytotoxic glycopeptide antibiotics Initiate ssDNA cleavage at pyrimidines 3' to a guanine, generating blunt/staggered ends, depending on the residue B is reactivated + reorganised after cleavage of the first strand of DNA - linker is key for this Bond rotation between the two thiazole tails makes the drug available for interaction with the second DNA strand

Question 47

Cisplatin

Answer 47

Intercalator Activated by water - it attacks the N7 of guanine Bends the DNA and makes it difficult to recognise for repair mechanisms

Question 48

Carboplatin

Answer 48

Second generation platinum agent (intercalator) Activated by water - it attacks the N7 of guanine Bends the DNA and makes it difficult to recognise for repair mechanisms Has a ligand that slows the release of the platinum moiety, leading to prolonged DNA binding and greater cytotoxicity.

Question 49

Oxaliplatin

Answer 49

Second generation platinum agent (intercalator) Activated by water - it attacks the N7 of guanine Bends the DNA and makes it difficult to recognise for repair mechanisms Has a diaminocyclohexane ligand that enhances the reactivity of the drug, forming more inter strand cross links.

Question 50

Doxorubicin

Answer 50

Intercalation that targets TOP2 Stabilises the top2 complex, producing a cleavable complex that results in DNA strand breakage

Question 51

NK314 (AR)

Answer 51

A new intercalator that targets TOP2a, a specific isoform. There is no therapeutic benefit in targeting TOP2b, as side effects such as cardiotoxicity and secondary malignancy can occur