Small molecule inhibitors selective for polo-like kinase proteins
Disclosed are small molecule PLK inhibitors that can target the polo box domain (PBD). Inhibitors can have an atomic mass of about 1000 Da or less and a general structure of For instance, the inhibitors can include an alkyl benzamido benzoic acid core structure.
1. A method for inhibiting Polo-Like Kinase (PLK) proteins, the method comprising:
providing a small molecule PLK inhibitor to a medium containing one or more PLK proteins, wherein the small molecule PLK inhibitor has the general structure:
wherein
R1 is an -S-alkyl; and
R 4 is an alkyl.
2. The method of claim 1 , wherein the medium comprises a solution.
3. The method of claim 1 , wherein the medium comprises one or more cells.
4. The method of claim 3 , wherein the one or more cells comprise HeLa cervical cancer cells, PTEN-deficient prostate cancer PC3 cells, KRAS mutant lung cancer A-549 cells, or a combination thereof.
5. The method of claim 1 , wherein the medium comprises one or more cells and the inhibitor induces apoptosis in a least a portion of the one or more cells.
6. The method of claim 1 , wherein the one or more Polo-like Kinase proteins comprise PLK3.
7. The method of claim 1 , wherein the one or more Polo-like Kinase proteins comprise PLK1.
8. The method of claim 1 , wherein the small molecule PLK inhibitor has an atomic mass of about 1000 Daltons or less.
9. The method of claim 1 , wherein the small molecule PLK inhibitor has an atomic mass of about 500 Daltons or less.
10. The method of claim 1 , wherein the small molecule PLK inhibitor has a polar surface area of about 200 Å or less.
11. The method of claim 1 , wherein the small molecule PLK inhibitor has a polar surface area of about 100 Å or less.
12. The method of claim 1 , wherein R4 is a methyl.