TABLE 2.
List of Relevant Hubs in Monocyte Gene-expression Modules Associated With Disease Behavior to Potentially Repurpose for Use as CD Drug-targets.
| Hub Protein Name | Hub Protein Description | Functions | Module Harboring the Hub (No. pathways enriched) | Representativs Reactome Pathways Enriched in the Module |
Drugs Targeting the Hub (Disease* - Clinical trial ID) |
|---|---|---|---|---|---|
| ADORA3 | Adenosine receptor A3 | Proinflammatory activation of monocytes91 | M4 (2) | G Alpha I signaling events, DAG and IP3 signaling | Piclidenoson (PS - NCT03168256,NCT00428974,NCT01265667) Piclidenoson (RA - NCT02647762,NCT00280917,NCT00556894, NCT01034306) Caffeine (UC - NCT02760615^) Caffeine (RA - NCT01636557, NCT03131973) |
| CXCR2 | C-X-C chemokine receptor type 2 | Recruitment of atherogenic and inflammatory monocytes92 Involved in the adhesion of monocytes to tissues and other cell types93 |
M2 (2) | IL-4 and IL-13 signaling | Navarixin (PS - NCT00684593) |
| FLT3 | Receptor-type tyrosine-protein kinase FLT3 | Involved in normal granulocyte-monocyte progenitor development94 Proliferation of monocytes95 |
M4 (2) | G Alpha I signaling events, DAG and IP3 signaling | Lestaurtinib (PS - NCT00236119) Pexidartinib (RA - NCT01090570^) Elubrixin (UC - NCT00748410^) |
| PRKCE | Protein kinase C epsilon type | Upregulated in monocytes96 | M4 (2) | G Alpha I signaling events, DAG and IP3 signaling | Sotrastaurin (PS -NCT00885196) Sotrastaurin (UC -NCT00572585) |
| IL1A | Interleukin-1 alpha | Induces interleukin 1 receptor antagonist production in human monocytes97 Involved in the cross-talk between monocytes and stromal98 |
M5 (13) | IL-10 signaling, NLR signaling | Bermekimab (PS -NCT01384630) |
| IL1R1 | Interleukin-1 receptor type 1 | Expressed in monocytes in response to LPS exposure99 | M6 (-) | - | Anakinra (RA - NCT00111410,NCT00121043, NCT00117091,NCT00037700, NCT00537667^) AMG-108 (RA - NCT00293826, NCT00369473) |
| CD40 | Tumor necrosis factor receptor superfamily member 5 | Induction of IL-1β and tumor necrosis factor-α synthesis100 Adhesion of monocytes to other cell types101 |
M9 (18) | Interferon-gamma signaling, Antigen processing cross presentation, IL-12 family signaling | PG-102(RA - NCT00787137^) |
*PS, psoriasis; RA, rheumatoid arthritis; UC, ulcerative colitis.
^Suspended, terminated or withdrawn clinical trials.