TABLE 2.
Significant compounds and pathways identified from the Reactome and Wilcoxon Rank sum test. Detailed information of the 83 compounds from the initial compound library that were shown to be significant in both the Reactome pathway analysis and wilcoxon rank sum test. The strictly standardized mean difference (SSMD) score measures the effect size and the variance amongst the triplicate larval samples for each compound. The brain health score (BHS) was defined as the logarithm of the covariance between the brain image and a template image. During the analysis pipeline, the SSMD and BHS scores were converted for directionality based on the pharmacological activity profile obtained from the Therapeutic Target database. The pathway names were outputted directly based on the target and activity profile from Reactome.
| Compound | Pathway name | SSMD | BHS | Target | Activity | FDA status |
|---|---|---|---|---|---|---|
| Dexmedetomidine | Adrenaline signalling through Alpha-2 adrenergic receptor | 1.040 | −2.928 | ADRA2A | AGONIST | Approved |
| Guanabenz Acetate | Adrenaline signalling through Alpha-2 adrenergic receptor | 0.984 | −0.868 | ADRA2A | AGONIST | Approved |
| Noradrenaline | Adrenaline signalling through Alpha-2 adrenergic receptor | 0.855 | −1.021 | ADRA2A | STIMULATOR | Approved |
| Phentolamine Mesylate | Adrenaline signalling through Alpha-2 adrenergic receptor | −0.818 | 0.624 | ADRA2A | INHIBITOR | Approved |
| Medetomidine | Adrenaline signalling through Alpha-2 adrenergic receptor | 0.777 | −0.729 | ADRA2A | AGONIST | Approved |
| Ivabradine HCl | Adrenaline signalling through Alpha-2 adrenergic receptor | 0.539 | 0.156 | ADRA2A | INHIBITOR | Approved |
| Y-27632 2HCl | Apoptosis | 4.834 | 0.694 | ROCK1 | INHIBITOR | |
| Oprozomib | Apoptosis | 1.558 | 0.221 | PSMB8 | INHIBITOR | |
| Apoptosis Activator 2 | Apoptosis | 1.291 | −3.112 | CASP3 | ACTIVATOR | |
| Evodiamine | Apoptosis | −1.150 | −0.525 | BCL2 | INDUCER | |
| RKI-1447 | Apoptosis | 1.124 | −0.097 | ROCK1 | INHIBITOR | |
| Dynasore | Apoptosis | 0.913 | −0.232 | DNM1 | INHIBITOR | |
| PF-573228 | Apoptosis | 0.891 | 0.305 | PTK2 | INHIBITOR | |
| Carfilzomib (PR-171) | Apoptosis | −0.801 | −0.066 | PSMD9 | AGONIST | Approved |
| ZSTK474 | Cell surface interactions at the vascular wall | 1.500 | 0.322 | PIK3CA | INHIBITOR | |
| Dactolisib (BEZ235, NVP-BEZ235) | Cell surface interactions at the vascular wall | 0.904 | 0.571 | PIK3CA | INHIBITOR | |
| RepSox | Cell surface interactions at the vascular wall | 0.746 | −0.112 | TGFB1 | INHIBITOR | |
| Dasatinib | Cell surface interactions at the vascular wall | 0.690 | 0.261 | SRC | INHIBITOR | Approved |
| ML347 | Cell surface interactions at the vascular wall | 0.625 | −0.090 | TGFB1 | INHIBITOR | |
| CAL-101 (Idelalisib, GS-1101) | Cell surface interactions at the vascular wall | 0.590 | 0.360 | PIK3CA | INHIBITOR | |
| Bosutinib (SKI-606) | Cell surface interactions at the vascular wall | 0.558 | 0.134 | SRC | INHIBITOR | Approved |
| Ibuprofen (Dolgesic) | COX reactions | 1.124 | 0.217 | COX | INHIBITOR | Approved |
| Mefenamic acid | COX reactions | 1.074 | 0.446 | COX | INHIBITOR | Approved |
| Etodolac (Lodine) | COX reactions | 0.988 | 1.390 | COX | INHIBITOR | Approved |
| Bromfenac | COX reactions | 0.778 | 1.053 | COX | INHIBITOR | Approved |
| Nepafenac | COX reactions | 0.773 | 1.227 | COX | INHIBITOR | Approved |
| Diclofenac Sodium | COX reactions | 0.694 | 0.428 | PTSG2 | INHIBITOR | Approved |
| Ketorolac (ketorolac tromethamine) | COX reactions | 0.577 | 0.504 | COX | INHIBITOR | Approved |
| Suprofen (Profenal) | COX reactions | 0.510 | 0.423 | COX | INHIBITOR | Approved |
| Enzastaurin (LY317615) | Depolymerisation of the Nuclear Lamina | 0.522 | 0.610 | PRKCB | INHIBITOR | |
| JTC-801 | G-protein activation | −1.223 | −3.519 | OPRM1 | ANTAGONIST | |
| Matrine ((+)-Matrine) | G-protein activation | 0.800 | 0.787 | OPRM1 | AGONIST | |
| Naloxone HCl | G-protein activation | 0.564 | 0.964 | OPRM1 | AGONIST | Approved |
| Tenovin-1 | G2/M DNA damage checkpoint | −1.612 | −0.715 | TP53 | ACTIVATOR | |
| VE-821 | G2/M DNA damage checkpoint | 0.923 | 0.332 | ATM | INHIBITOR | |
| VE-822 | G2/M DNA damage checkpoint | 0.781 | 0.041 | ATR | ANTAGONIST | |
| LY2608204 | Glycolysis | 1.145 | 1.058 | GCK | INHIBITOR | |
| Clorsulon | Glycolysis | 0.907 | 0.518 | GPM1 | INHIBITOR | |
| Vismodegib (GDC-0449) | Hh mutants that don’t undergo autocatalytic processing are degraded by ERAD | 1.472 | 0.739 | SHH | INHIBITOR | Approved |
| PNU-120596 | Highly calcium permeable nicotinic acetylcholine receptors | −1.142 | −3.868 | CHRNA1 | AGONIST | |
| Tropicamide | Highly calcium permeable nicotinic acetylcholine receptors | 0.952 | 0.697 | CHRNA1 | INHIBITOR | Approved |
| Darifenacin | Highly calcium permeable nicotinic acetylcholine receptors | 0.869 | 0.064 | CHRNA1 | INHIBITOR | Approved |
| Pancuronium dibromide | Highly calcium permeable nicotinic acetylcholine receptors | 0.860 | 0.930 | CHRNA1 | INHIBITOR | Approved |
| Gallamine triethiodide (Flaxedil) | Highly calcium permeable nicotinic acetylcholine receptors | 0.685 | 1.034 | CHRNA1 | INHIBITOR | Approved |
| Adiphenine | Highly calcium permeable nicotinic acetylcholine receptors | 0.671 | 0.306 | CHRNA1 | INHIBITOR | |
| Bethanechol chloride | Highly calcium permeable nicotinic acetylcholine receptors | 0.570 | −0.201 | CHRNA1 | AGONIST | Approved |
| Atropine sulfate monohydrate | Highly calcium permeable nicotinic acetylcholine receptors | 0.551 | 0.416 | CHRNA1 | INHIBITOR | Approved |
| Cytisine | Highly calcium permeable nicotinic acetylcholine receptors | −0.520 | −0.750 | CHRNA4 | AGONIST | |
| Aliskiren hemifumarate | Metabolism of Angiotensinogen to Angiotensins | 1.540 | 1.1308 | REN | INHIBITOR | Approved |
| Imidapril HCl | Metabolism of Angiotensinogen to Angiotensins | 0.938 | 0.5801 | ACE | INHIBITOR | |
| Enalapril Maleate | Metabolism of Angiotensinogen to Angiotensins | 0.860 | 2.947 | ACE | INHIBITOR | |
| Quinapril hydrochloride (accupril) | Metabolism of Angiotensinogen to Angiotensins | 0.707 | 0.385 | ACE | INHIBITOR | Approved |
| Ramipril | Metabolism of Angiotensinogen to Angiotensins | 0.498 | 0.253 | ACE | INHIBITOR | Approved |
| SB590885 | Negative feedback regulation of MAPK pathway | 1.699 | 0.738 | RAF1 | INHIBITOR | |
| Selumetinib (AZD6244) | Negative feedback regulation of MAPK pathway | 1.098 | 0.172 | MEK1 | INHIBITOR | |
| RAF265 (CHIR-265) | Negative feedback regulation of MAPK pathway | 0.886 | 0.537 | RAF1 | INHIBITOR | |
| SL327 | Negative feedback regulation of MAPK pathway | 0.812 | 0.668 | MEK1 | INHIBITOR | |
| Vemurafenib (PLX4032, RG7204) | Negative feedback regulation of MAPK pathway | 0.625 | 0.962 | BRAF | INHIBITOR | Approved |
| Tanshinone IIA (Tanshinone B) | Negative feedback regulation of MAPK pathway | 0.547 | 1.823 | MAP2K1 | INHIBITOR | |
| PD0325901 (PD325901) | Negative feedback regulation of MAPK pathway | 0.511 | 0.597 | MEK1 | INHIBITOR | |
| IWR-1 (endo-IWR 1) | PCP/CE pathway | 2.195 | 0.994 | WNT1 | INHIBITOR | |
| EHop-016 | PCP/CE pathway | 0.879 | −0.273 | RAC1 | INHIBITOR | |
| XAV-939 | PCP/CE pathway | 0.544 | 0.853 | WNT1 | INHIBITOR | |
| Protionamide | Peptide hormone metabolism | 1.636 | 0.710 | INHA | INHIBITOR | |
| Alogliptin | Peptide hormone metabolism | 0.988 | 0.720 | DPP4 | INHIBITOR | Approved |
| TAK-875 | Peptide hormone metabolism | 0.733 | 1.320 | gpr40 | ANTAGONIST | |
| SGC-CBP30 | Regulation of Hypoxia-inducible Factor (HIF) by oxygen | 2.312 | 1.079 | DOT1L | INHIBITOR | |
| Rapamycin | Regulation of TP53 Activity | 1.679 | 1.365 | MTOR | INHIBITOR | Approved |
| P22077 | Regulation of TP53 Activity | 1.145 | 0.694 | USP7 | INHIBITOR | |
| ETP-46464 | Regulation of TP53 Activity | 1.085 | 0.023 | MTOR | INHIBITOR | |
| Ridaforolimus | Regulation of TP53 Activity | 1.078 | 0.298 | MTOR | INHIBITOR | |
| PP242 | Regulation of TP53 Activity | 0.896 | 0.892 | MTOR | INHIBITOR | |
| KU-0063794 | Regulation of TP53 Activity | 0.618 | 1.254 | MTOR | INHIBITOR | |
| PHT-427 | Regulation of TP53 Activity | 0.616 | 0.553 | AKT1 | INHIBITOR | |
| Entinostat (MS-275) | Regulation of TP53 Activity | 0.574 | 0.524 | HDAC1 | INHIBITOR | |
| AZD1152-HQPA (Barasertib) | Regulation of TP53 Activity | 0.517 | 1.01 | AURKB | INHIBITOR | |
| Carprofen | Respiratory electron transport | 0.697 | 0.858 | cox2 | INHIBITOR | Approved |
| Cilengitide | Smooth Muscle Contraction | 0.718 | −0.104 | ITGA1 | INHIBITOR | |
| (-)-Huperzine A | Synthesis of PC | 1.320 | 0.550 | ACHE | INHIBITOR | |
| Odanacatib (MK 0822) | Toll-Like Receptors Cascades | −1.054 | −0.098 | CTSK | AGONIST | |
| EUK 134 | Toll-Like Receptors Cascades | 0.529 | 0.279 | APP | INHIBITOR | |
| NMDA | TP53 Regulates Metabolic Genes | 1.691 | 0.619 | NMDA | AGONIST | |
| BAM 7 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 0.763 | 0.027 | BAX | INDUCER | |