DNA Cleaving Agents/Topo Inhibitors

Question 1

Topo1 inhibitor MOA

Answer 1

Single strand breakers. Bind only when Topo1 is bound to the DNA.

Question 2

Topo1i agents

Answer 2

Campothecin
Ironotecan
Topotecan

Question 3

Campothecin

Answer 3

binds with DNA bases and amino acid side chains of Topo1. Not FDA approved. SEE #43!!
Guanine on scissile strand, Cytosine on non-cleaved strand of DNA
Arg364, Asp533, Asn722 of Topo1
Only the upper left can be modified! (rings A/B)

Question 4

Topo2i MOA

Answer 4

double strand break. Bind only to Topo2 when its bound to the DNA
Cell cycle specific: S and G2. See #47 for SAR
Problem is that if resistant tumor cells may already be resistant to Topo2 inhibitors

Question 5

Topo2i agents

Answer 5

Etoposide

Teniposide