Table 7.
The 10 top-ranked compounds as drug targets for ALK, EGLN3, and NUAK1.
| DrugBank ID | Compound name | Representative target cancer genes |
|---|---|---|
| ALK | ||
| DB01933 | 7-Hydroxystaurosporine | PDK1 |
| DB08700 | 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy] | ALK, c-MET, LCK, |
| -5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-2-amine | TRKA, TRKB, TIE2, ABL | |
| DB04651 | BIOTINOL-5-AMP | -- |
| DB02491 | 4-[4-(1-Amino-1-Methylethyl)Phenyl]-5-Chloro-N | FGFR2 |
| -[4-(2-Morpholin-4-Ylethyl)Phenyl]Pyrimidin-2-Amine | ||
| DB07006 | 9-HYDROXY-6-(3-HYDROXYPROPYL)-4 | WEE1 |
| -(2-METHOXYPHENYL)PYRROLO[3,4-C] | ||
| CARBAZOLE-1,3(2H,6H)-DIONE | ||
| DB02010 | Staurosporine | ITK, SYK, MAPKAPK2, GSK3, |
| CSK, CDK, PIK3CG, ZAP-70 | ||
| DB02654 | 6-Hydroxy-Flavin-Adenine Dinucleotide | -- |
| DB07460 | 2-({5-CHLORO-2-[(2-METHOXY-4-MORPHOLIN | ALK, PTK2 |
| -4-YLPHENYL)AMINO]PYRIMIDIN-4 | ||
| -YL}AMINO)-N-METHYLBENZAMIDE | ||
| DB07186 | 4-(4-METHYLPIPERAZIN-1-YL)-N-[5 | AURKA, PLK1 |
| -(2-THIENYLACETYL)-1,5-DIHYDROPYRROLO | ||
| [3,4-C]PYRAZOL-3-YL]BENZAMIDE | ||
| DB03247 | Riboflavin Monophosphate | RPS6KA4, POR(P450), SGK1, |
| NOS1, DPYD, DHODH | ||
| EGLN3 (with Fe) | ||
| DB03702 | 2-[4-[[(S)-1-[[(S)-2-[[(Rs)-3,3,3-Trifluoro-1-Isopropyl-2 | CELA1 |
| -Oxopropyl]Aminocarbonyl]Pyrrolidin-1-Yl-]Carbonyl]-2 | ||
| -Methylpropyl]Aminocarbonyl]Benzoylamino]Acetic Acid | ||
| DB04761 | PYRIMIDINE-4,6-DICARBOXYLIC ACID | MMP13 |
| BIS-[(PYRIDIN-3-YLMETHYL)-AMIDE] | ||
| DB08687 | N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL) | EGLN1, PHD2 |
| CARBONYL]GLYCINE | ||
| DB08131 | 2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H | thyA |
| -PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL] | ||
| -BENZOYLAMINO}-3-METHYL-BUTYRIC ACID | ||
| DB02718 | 5-Formyl-6-Hydrofolic Acid | -- |
| DB02015 | Dihydrofolic Acid | -- |
| DB02031 | (6s)-5,6,7,8-Tetrahydrofolate | NOS1, thyA |
| DB04760 | PYRIMIDINE-4,6-DICARBOXYLIC ACID | MMP13 |
| BIS-(4-FLUORO-3-METHYL-BENZYLAMIDE) | ||
| DB04759 | PYRIMIDINE-4,6-DICARBOXYLIC ACID | MMP13 |
| BIS-(3-METHYL-BENZYLAMIDE) | ||
| DB07112 | N-[(4-HYDROXY-8-IODOISOQUINOLIN-3-YL) | EGLN1, PHD2 |
| CARBONYL]GLYCINE | ||
| EGLN3 (without Fe) | ||
| DB08687 | N-[(1-CHLORO-4-HYDROXYISOQUINOLIN | EGLN1, PHD2, HIF1A |
| -3-YL)CARBONYL]GLYCINE | ||
| DB03702 | already listed in EGLN3 (with Fe) | |
| DB04759 | already listed in EGLN3 (with Fe) | |
| DB03625 | 5,10-Dideazatetrahydrofolic Acid | GARFTase |
| DB04760 | already listed in EGLN3 (with Fe) | |
| DB07112 | already listed in EGLN3 (with Fe) | |
| DB02015 | already listed in EGLN3 (with Fe) | |
| DB03541 | 10-Propargyl-5,8-Dideazafolic Acid | TYMS, DHFR |
| DB00158 | Folic Acid | -- |
| DB04761 | already listed in EGLN3 (with Fe) | |
| NUAK1 | ||
| DB08053 | 1-cyclobutyl-3-(3,4-dimethoxyphenyl)-1H | CSF1R and others |
| -pyrazolo[3,4-d]pyrimidin-4-amine | ||
| DB08052 | 1-cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl) | CSF1R and others |
| -1H-pyrazolo[3,4-d]pyrimidin-4-amine | ||
| DB08054 | 1-(1-methylethyl)-3-quinolin-6-yl-1H | CSF1R and others |
| -pyrazolo[3,4-d]pyrimidin-4-amine | ||
| DB07563 | 1-{7-cyclohexyl-6-[4-(4-methylpiperazin-1-yl) | CTSK |
| benzyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}methanamine | ||
| DB08035 | 1-TERT-BUTYL-3-(2,5-DIMETHYLBENZYL) | AR |
| -1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE | ||
| DB04463 | 3-(4-Amino-1-Tert-Butyl-1h-Pyrazolo[3,4-D] | CBR1 |
| Pyrimidin-3-Yl)Phenol | ||
| DB08300 | 1-methyl-3-naphthalen-2-yl-1H-pyrazolo | CSF1R and others |
| [3,4-d]pyrimidin-4-amine | ||
| DB01809 | 1-Ter-Butyl-3-P-Tolyl-1h-Pyrazolo | PKD1 and others |
| [3,4-D]Pyrimidin-4-Ylamine | ||
| DB08461 | 3-[(4-AMINO-1-TERT-BUTYL-1H-PYRAZOLO[3,4-D] | AR |
| PYRIMIDIN-3-YL)METHYL]PHENOL | ||
| DB08699 | 1-tert-butyl-3-(3-methylbenzyl)-1H-pyrazolo | CAMK2G |
| [3,4-d]pyrimidin-4-amine | ||
The compounds were ranked based on FPAScores averaged over three independent trials and their representative target cancer genes. For the full lists of ranked compounds and a detailed discussion of the target cancer genes listed here, see Additional files 7 and 8, respectively. ALK and EGLN1, a paralog of EGLN3, are in bold letters. "―" indicates that no known cancer-associated genes are targeted by these compounds.