Cytosine-based TET enzyme inhibitors
Provided herein, in some embodiments, are cytosine analogs, compositions comprising cytosine analogs, and methods of use for inhibiting a Ten-eleven translocation (TET) enzyme.
1. A composition comprising a cytosine analog of forma I
or a pharmaceutically acceptable salt thereof,
wherein R 1 is independently selected from the group consisting of hydrogen, halogen, and an unsubstituted methyl, and
wherein R 2 is selected from the group consisting of an optionally substituted phenyl or pyridyl group, and
wherein the cytosine analog is in an amount effective to inhibit a Ten-eleven translocation (TET) enzyme.
2. The composition of claim 1 , wherein R 1 is hydrogen.
3. The composition of claim 1 , wherein R 1 is halogen.
4. The composition of claim 1 , wherein R 1 is methyl.
5. The composition of claim 3 , wherein R 1 is Cl.
6. The composition of claim 1 , wherein R 2 is optionally substituted phenyl.
7. The composition of claim 6 , wherein the optionally substituted phenyl is substituted with halogen, optionally substituted C 1-6 alkyl, or phenyl.
8. The composition of claim 6 , wherein R 2 is unsubstituted phenyl, 4-chlorophenyl, 3-chlorophenyl, 2-biphenyl, 3-biphenyl, 4-biphenyl, or 4-methylphenyl.
9. The composition of claim 1 , wherein R 2 is optionally substituted pyridyl.
10. The composition of claim 1 , wherein the cytosine analog of formula I is selected from the group consisting of:
and a pharmaceutically acceptable salt of one of the aforementioned compounds.
11. A method for inhibiting a Ten-eleven translocation (TET) enzyme, the method comprising contacting the composition of claim 1 with the TET enzyme.
12. The method of claim 11 , wherein the TET enzyme is TET1, TET2 or TET3.
13. The method of claim 11 , wherein the contacting occurs in vitro or in vivo.