Podophyllotoxin derivatives and their use

1. A compound of formula (I):

or an N-oxide thereof, or a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing, wherein

R 1 is H or has a structure of:

R 3 is H, an optionally substituted C 1 -C 8 alkyl, an optionally substituted 3-10 membered cycloalkyl, an optionally substituted 3-10 membered heterocyclyl, an optionally substituted 6-10 membered aryl, or an optionally substituted 5-10 membered heteroaryl;

R 5 is H or has a structure of:

 and

R 11 and R 12 independently is an optionally substituted C 1 -C 8 alkyl.

2. The compound of claim 1 , wherein R 1 is H.

3. The compound of claim 1 , wherein R 1 has the structure of:

4. The compound of claim 1 , wherein R 3 is H.

5. The compound of claim 1 , wherein R 5 is:

6. The compound of claim 1 , wherein R 11 and R 12 independently is C 1 -C 8 alkyl.

7. The compound of claim 6 , wherein R 11 is methyl and R 12 is methyl.

8. The compound of claim 1 , wherein R 5 is H.

9. The compound of claim 1 , wherein R 3 is C 1 -C 8 alkyl.

10. The compound of claim 1 , wherein R 3 is an ethyl.

11. The compound of claim 1 selected from the group consisting of:

or an N-oxide thereof, or a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing.

12. A pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutically acceptable excipient.

13. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition is a solid form, liquid form, injectable form, or a liposomal formulation.

14. A pharmaceutical composition comprising a compound of claim 11 and at least one pharmaceutically acceptable excipient.

15. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition is a solid form, liquid form, injectable form, or a liposomal formulation.