Table 3.
Major CDK inhibitors.
| Inhibitor | Type/Nature/Class | Target | References |
|---|---|---|---|
| ATP-competitive compounds | |||
| Butyrolactone I | ATP-competitive/natural product | CDK1 > CDK2 | [290,291,292,293] |
| Staurosporine | ATP-competitive/alkaloid | CDK1, CDK2, CDK4 | [294,295] |
| 7-hydroxystaurosporine/UCN01 | ATP-competitive/alkaloid | CDK2, pRb, Chk1 | [270,296,297] |
| Flavopiridol/Alvocidib | ATP-competitive/flavonoid | CDK2, CDK4, CDK6, CDK9 | [270,298,299,300,301,302,303,304] |
| P276-00 | ATP-competitive/flavone | CDK1, CDK4, CDK9 | [305,306] |
| Hymenialdisine | ATP-competitive/natural product | CDK5, GSK3beta, CDK2, CDK1, Chk1 | [307] |
| Fascaplysine | ATP-competitive/natural product | CDK4 | [308] |
| Meriolins | ATP-competitive/aminopyrimidine indole | CDK1, CDK4, CDK9 | [309] |
| Roscovitine/CYC202/Seliciclib/CYC065 | ATP-competitive/trisubstituted purine | CDK5, CDK2, CDK1, CDK7, CDK9 | [310,311,312,313,314,315] |
| NU2058 & NU6027 | ATP-competitive/purine/pyrimidine | CDK1, CDK2 | [316,317] |
| Purvalanol-A | ATP-competitive/purine | CDK1,2, 5 | [318,319] |
| NU6140 | ATP-competitive/purine | [320] | |
| Olomoucine | ATP-competitive/purine | CDK1, CDK2, CDK5 | [321,322] |
| Indirubin-5 | ATP-competitive/indolinone | CDK1 > CDK2 > CDK5 | [323,324] |
| SU9516 | ATP-competitive/3-substituted indolinone | CDK2, CDK4 | [325,326] |
| Paullones | ATP-competitive/paullone | CDKs | [323,324,327] |
| R547/Ro-4584820 | ATP-competitive/Diaminopyrimidine | CDK1, CDK2, CDK4 | [328,329,330] |
| Dinaciclib (SCH 727965) | ATP-competitive/pyrimidine | CDK9, CDK1, CDK2, CDK5 | [331,332,333,334] |
| CDKI-73 | ATP-competitive/pyrimidine | CDK9 | [335] |
| PD-0183812 | ATP-competitive/pyridine | CDK4, CDK6 | [336] |
| PD-0322991/Palbociclib | ATP-competitive/pyrido-pyrimidine | CDK4, CDK6 | [337,338,339,340,341,342] |
| LEE011/LY2835219 | Small molecule | CDK1, CDK2, CDK4 | [343,344,345] |
| SNS-032/BMS-387032 | ATP-competitive/thiazole | CDK2, CDK7, CDK9 | [346,347] |
| RO-3306 | ATP-competitive/thiazolinone | CDK1 > CDK2 | [348] |
| AT7519 | ATP-competitive/pyrazole | CDK2, CDK9, CDK5, CDK4 | [349,350,351,352] |
| Peptides Targeting PPI | |||
| Spa310 and derivative from p130/pRb spacer domain | Peptide Competing with Substrate | CDK2/Cyclin A | [353,354] |
| CIP Peptide derived from p53, targeting CDK2/p53 | Peptide Competing with Substrate | CDK2/Cyclin A | [355] |
| C4 interface peptide derived from Cyclin A | Peptide Targeting CDK/Cyclin PPI | CDK2/CyclinA | [356] |
| NBI1 hexapeptide targeting Cyclin A surface pocket | Peptide Targeting CDK/Cyclin PPI | CDK2/Cyclin A | [357] |
| Interface Peptides derived from p35: CIP and p5 | Peptide Targeting CDK/Cyclin PPI | CDK5/p35 | [358,359,360,361,362,363] |
| RXL peptides | Peptide Targeting Cyclin-binding Groove | CDK2/CyclinA | [364] |
| C-terminal hexapeptide PRGPRP | Peptides Targeting CDK4 | CDK4/Cyclin D | [365] |
| Small peptides derived from E2F1 | Peptide Targeting Cyclin-binding Groove | CDK2 | [366] |
| Peptides derived from p21 | Peptide Targeting Cyclin-binding Groove | CDK2, CDK4 | [367,368,369,370,371,372] |
| Peptides derived from p27 | Peptide Targeting Cyclin-binding Groove | CDK2, CDK4 | [373] |
| Cyc103/cyclic peptide derived from p27 | Peptide Targeting Cyclin-binding Groove | CDK2 | [374] |
| Constrained peptidomimetic of p27 peptide | Peptide Targeting Cyclin-binding Groove | CDK2 | [375] |
| Peptide derived from P16INK4 | Peptide Targeting Cyclin-binding Groove | CDK4, CDK6 | [376,377] |
| ATP-Non Competitive Small molecules | |||
| SU9516 | ATP-competitive/3-substituted indolinone | CDK4 | [325,326] |
| Compound 1 | Small Molecule | CDK4 | [378] |
| 3-ATA: 3-amino thioacridone | Aminoacridines | CDK4 | [379] |
| CPD1—3alpha-amino-5alpha androstane | Small Molecule Non-ATP competitive | CDK5/p35 | [380,381] |
| Allosteric pocket in CDK2/CyclinA/p27 | Small Molecule Non-ATP competitive | CDK2/cyclinA/p27 | [382] |
| Chrysin-derivative/compound 69407 | Small Molecule Non-ATP competitive Allosteric | CDK2 & CDK4/CDK6 | [383] |
| ZK304709/MTGI/ZK-CDK | ATP-competitive | CDK1, CDK2,CDK4, CDK7, CDK9 | [384,385] |
| Cki-277 | ATP-competitive/thiazole urea | CDK1, CDK2 | [386] |
| JNJ-7706621 | ATP-competitive/acyl-substitutes triazole diamine | CDK1, CDK2/Aurora kinases | [387,388] |
| RGB-286199 | ATP-competitive/indenopyrazole | ||
| AG-024322 | Drug-like | CDK1, CDK2, CDK4 | [389] |
| AZD5438 | Drug-like | CDK1, CDK2, CDK9 | [390,391] |
| PHA-848125 | Drug like | CDK2 | |
| PHA-793887 | Drug like | CDK1, CDK2, CDK5, CDK7, CDK9 | |
| BAY-1000394 | Drug like | CDK1, CDK4, CDK9 | |
| CINK4 | ATP-competitive/triamino-pyrimidine | CDK4, CDK6 | [392] |
| 2-Aminoquinazoline inhibitors | Small molecule | CDK4 | [393] |
| 7X | Cyanopyridopyrimidine | CDK4 (ARK5) | [394] |
| Small molecule | CDK2, CDK4 | [395] | |