Table 1.
Compounds positively correlated with LKB1 mutation signature
| Compound | # Probesets in CMAP DE signatures | # Probesets in compound signature | # Probesets in signature | # CMAP DE probesets in signature | # Overlap | % Overlap | Tanimoto similarity | Fisher’s exact test | Quadrant count tatio | P signs | Score |
|---|---|---|---|---|---|---|---|---|---|---|---|
| colforsin* | 18255 | 562 | 130 | 120 | 26 | 21.7 | 0.0396 | 2.58E-15 | 0.846 | 1.05E-05 | 168.8 |
| salbutamol† | 18255 | 325 | 130 | 120 | 20 | 16.7 | 0.0471 | 3.09E-14 | 1.000 | 1.91E-06 | 164.7 |
| alprostadil‡ | 18255 | 1001 | 130 | 120 | 24 | 20.0 | 0.0219 | 2.27E-08 | 0.750 | 2.77E-04 | 116.5 |
| dinoprostone‡ | 18255 | 484 | 130 | 120 | 17 | 14.2 | 0.0290 | 1.56E-08 | 0.882 | 2.75E-04 | 111.3 |
| (-)-isoprenaline† | 18255 | 203 | 130 | 120 | 12 | 10.0 | 0.0386 | 8.69E-09 | 0.833 | 6.35E-03 | 92.7 |
| 15(S)-15-methylprostaglandin E2‡ | 18255 | 334 | 130 | 120 | 13 | 10.8 | 0.0295 | 2.66E-07 | 0.846 | 3.42E-03 | 89.4 |
| 16,16-dimethylprostaglandin E2‡ | 18255 | 322 | 130 | 120 | 12 | 10.0 | 0.0279 | 1.22E-06 | 0.833 | 6.35E-03 | 81.6 |
| phenoxybenzamine§ | 18255 | 2018 | 130 | 120 | 24 | 20.0 | 0.0114 | 1.53E-03 | 0.583 | 6.61E-03 | 72.1 |
| isoxsuprine† | 18255 | 235 | 130 | 120 | 10 | 8.3 | 0.0290 | 3.05E-06 | 0.800 | 2.15E-02 | 70.8 |
| 16-phenyltetranorprostaglandin E2‡ | 18255 | 400 | 130 | 120 | 10 | 8.3 | 0.0196 | 2.44E-04 | 1.000 | 1.95E-03 | 69.3 |
| menadioneǁ | 18255 | 705 | 130 | 120 | 14 | 11.7 | 0.0173 | 1.60E-04 | 0.714 | 1.29E-02 | 67.9 |
| 11-deoxy-16,16-dimethylprostaglandin E2‡ | 18255 | 723 | 130 | 120 | 14 | 11.7 | 0.0169 | 2.05E-04 | 0.714 | 1.29E-02 | 67.2 |
| corbadrine† | 18255 | 177 | 130 | 120 | 9 | 7.5 | 0.0313 | 2.30E-06 | 0.778 | 3.91E-02 | 66.5 |
| metaraminol† | 18255 | 179 | 130 | 120 | 7 | 5.8 | 0.0240 | 1.58E-04 | 1.000 | 1.56E-02 | 58.3 |
| ritodrine† | 18255 | 208 | 130 | 120 | 7 | 5.8 | 0.0218 | 3.82E-04 | 1.000 | 1.56E-02 | 56.0 |
| chlortetracycline¶ | 18255 | 1198 | 130 | 120 | 13 | 10.8 | 0.0100 | 2.55E-02 | 0.692 | 2.25E-02 | 48.0 |
| calmidazolium¶ | 18255 | 526 | 130 | 120 | 9 | 7.5 | 0.0141 | 5.46E-03 | 0.778 | 3.91E-02 | 47.3 |
* Water-soluble forskolin. All compounds identified in the CMAP screen with a quadrant count ratio >0.5 listed in rank order of overall score of correlation with LKB1-null signature.
† β-adrenergic receptor agonists.
‡ Prostaglandin E (PGE) analogues.
§ α-adrenergic receptor antagonist.
‖ Unknown mechanism. However, exposure to menadione is associated with activation of PGC1alpha, the major downstream target for CRTC1/CREB, suggesting a possible role as a CRTC1 activator (Gleyzer N, Scarpulla RC. J Biol Chem. 22;288(12):8004–8015, 2013).
¶ Regulate intracellular calcium channel flow.