Table 4.
New drug discovery/repurposing leads
| A. CMAP analysis with nominally validated biomarkers (22 increased and 118 decreased were present in HG-U133A array used by Connectivity Map) | ||
|---|---|---|
| Rank | cmap name | Score |
| 6100 | cefotiam | −1 |
| 6099 | proguanil | −0.991 |
| 6098 | hydroxyachillin | −0.96 |
| 6097 | Prestwick-682 | −0.95 |
| 6096 | levopropoxyphene | −0.949 |
| 6095 | isoflupredone | −0.943 |
| 6094 | ozagrel | −0.941 |
| 6093 | streptozocin | −0.938 |
| 6092 | cyclopenthiazide | −0.934 |
| 6091 | metformin | −0.93 |
| 6090 | corticosterone | −0.925 |
| 6089 | calcium folinate | −0.924 |
| 6088 | diphenhydramine | −0.921 |
| B. CMAP analysis with biomarkers that are nominally predictive in all (5 increased and 52 decreased were present in HG-U133A array used by Connectivity Map) | ||
|---|---|---|
| Rank | cmap name | Score |
| 6100 | ambroxol | −1 |
| 6099 | ozagrel | –0.971 |
| 6098 | cefotiam | −0.959 |
| 6097 | xamoterol | −0.951 |
| 6096 | betulin | −0.93 |
| 6095 | isometheptene | −0.927 |
| 6094 | primidone | −0.925 |
| 6092 | tocainide | −0.919 |
| 6093 | diloxanide | −0.919 |
| 6089 | alprostadil | −0.913 |
| 6090 | amphotericin B | −0.913 |
| 6087 | oxolamine | −0.909 |
| C. CMAP analysis with biomarkers that are nominally predictive in males (5 increased and 48 decreased were present in HG-U133A array used by Connectivity Map) | ||
|---|---|---|
| Rank | cmap name | Score |
| 6100 | ozagrel | −1 |
| 6099 | flucloxacillin | −0.981 |
| 6098 | ambroxol | −0.97 |
| 6097 | dapsone | −0.958 |
| 6096 | tiaprofenic acid | −0.955 |
| 6095 | primidone | −0.939 |
| 6094 | betulin | −0.936 |
| 6093 | proguanil | −0.929 |
| 6092 | gossypol | −0.925 |
| 6091 | levopropoxyphene | −0.92 |
| 6090 | xamoterol | −0.917 |
| 6089 | streptozocin | −0.912 |
| 6088 | tocainide | −0.909 |
| D. CMAP analysis with biomarkers that are nominally predictive in females (9 increased and 21 decreased were present in HG-U133A array used by Connectivity Map) | ||
|---|---|---|
| rank | cmap name | Score |
| 6100 | flecainide | −1 |
| 6099 | Prestwick-682 | −0.997 |
| 6098 | spiramycin | −0.98 |
| 6097 | domperidone | −0.974 |
| 6096 | homatropine | −0.967 |
| 6094 | isoniazid | −0.964 |
| 6095 | proguanil | −0.964 |
| 6093 | phentolamine | −0.958 |
| 6092 | sulfamonomethoxine | −0.952 |
| 6091 | fludrocortisone | −0.951 |
| 6090 | dizocilpine | −0.946 |
| 6087 | adiphenine | −0.942 |
| 6088 | tolnaftate | −0.942 |
Connectivity Map [66] (CMAP) analysis—drugs that have opposite gene expression profile effects to the signature of our validated genes (A), and out of them, those that are also significant predictive biomarkers (B–D). A score of −1 indicates the perfect opposite match, i.e., the best potential therapeutic to decrease stress. Bold—top candidates. Bold and italic—natural compounds of interest. Bold and underlined—compounds known to modulate stress, which serve as reassuring positive controls