Table 1.
DYRK1A inhibitors. The table shows the IC50 of different classes of DYRK1A inhibitors against DYRK1A, other DYRK proteins, and different kinases (only targets with submicromolar IC50 values are included). Cancer-related studies performed with those inhibitors are also indicated
| Compound name | IC50 (nM) |
Evidence related to cancer | |||
|---|---|---|---|---|---|
| (Chemical class) | DYRK1A | Other targets | therapy | Refs. | |
| Natural inhibitors | Harmine (β-carboline) | 22–400 | DYRK1B (166–300), DYRK2 (900–1,900), DYRK3 (800–1000), DYRK4 (80,000), MAO-A (5), CLK1 (27) | Angiogenesis inhibition; Cytotoxic activity in tumor cell lines in vitro (glioma, leukemia, colon, gastric, liver), and in vivo (glioma) |
101,107,111–115,117 |
| EGCG (Polyphenol) | 40–330 | Vimentin (3), COMT (70) | Clinical trials on cancer: urothelial, bladder, prostate, myeloma, breast, lung | 124,132,133 | |
| Staurosporine (glycosilated indolocarbazole) | 20 | Aurora A (7.2), Aurora B (20), Chk1 (1), Ftl3 (3), HGK (1), Ikkb (0.5), Jak2 (1), KDR (10), SYK (4) | 134 | ||
| Synthetic inhibitors | Lamerallins (Chromenoindole) | 40–5,000 | CDK5 (720->10,000), GSK3 (310->10,000), CDK1/CyclinB, PIM1, CK1 (70–8,000) | Apoptosis induction and multidrug resistance phenotype reversion | 119–121,135 |
| INDY (Benzothiazol) | 200 | DYRK1B (240) | Antiproliferative in gliomas | 101,118 | |
| Meriolins (Pyrimidinylindol/azaindol) | 30 | CDK1 (7–170), CDK2 (3–18), CDK5 (3–170), CDK9 (5.6–18), GSK3 (21–400), CK1 (50–200) | Antiproliferative and proapoptotic effects in tumor cells and glioma xenografts | 122,123 | |
| Variolin B (Pyrimidinylindol/azaindol) | 80 | CDK1 (60), CDK2 (80) CDK5 (90) CDK9 (26) GSK3 (70) CK1 (5) | 122 | ||
| Meridianins (Pyrimidinylindol/azaindol) | 34–900 | CDK5 (680->10,000), CK1 (490->10,000), CLK1 (30–70) | 136,137 | ||
| KHCB19 (dichloroindol) | 55 | CLK1 (20), CLK3 (500) | 138 | ||
| Imidazolone (Leucettamine) | 70–1,000 | CLK1 (15–71), GSK3(21–38) | 139 | ||
| Promiscuous kinase inhibitors | Purlavanol A (Purine) | 300 | CDK2 (30–100), PAK4 (100), SRC (<100 ), CDK2/CyclinA (100) | 107,124 | |
| A-443654 (Pyridine) | <10 | DYRK2, DYRK3 (<100 ), ERK8, RSK1, RSK2, PKBα, PKBβ, S6K1, PKA, ROCK2, PRK2, PKCa,PKD1,MSK1, SmMLCK, SK3b, CDK2-CyclinA, PIM1,2,3,MST2,HIPK2 (<100 ) | Initially identified as a potent Akt inhibitor for use in anticancer research field | 140 | |
| TBB, TBI, DMAT, TDI (Tetrahalo-bicycles) | 100–10,000 | DYRK2 (300–35,000), DYRK3 (2,000–5,000), CK2 (100–600), PIM1 (100–1,000), PIM2 (200–4,000), PIM3 (70–1,000) | 117,141–143 | ||