Table 1.

Characteristics of cellular signaling inhibitors.

Type of cellular signaling inhibitors	Characteristic	Example
JAK inhibitors	• Suppress the release of proinflammatory cytokines from the cell (85). • Approved for rheumatoid arthritis therapy. Small‐molecule JAK inhibitors are a novel category of drugs tested in clinical trials for immune‐mediated diseases and cancer (84).	Tofacitinib
Calcineurin inhibitors	• Act via suppressing T-cell activation (86, 87). • Used as an adjuvant to drugs for the prophylaxis of allogeneic post-transplant organ rejection (89) or after allogeneic organ grafts (88). • Calcineurin inhibitors are used for treating chronic atopic dermatitis (95).	Cyclosporine Tacrolimus
mTOR inhibitors	• mTOR regulates cell growth and proliferation, also associated with immune cell differentiation in immune regulation (96). • Show high antitumor activity in clinical studies. They are also used in combination with other antitumor drugs with a significant effect (90).	Sirolimus Everolimus
IMPDH inhibitors	• IMPDH is involved in purine metabolism and cell proliferation (97). Its activity is intensified in tumorigenesis (98). • Approved for a wide range of clinical uses such as the prevention of organ transplant rejection and antiviral agents and other indications including cancer and pathogenic microorganisms (91).	Azathioprine Leflunomide Mycophenolate
TACE inhibitors	• TACE is an enzyme that converts TNF-α and releases TNF-α related to the membrane (99, 100). • TACE inhibitors are promising and used in the clinic in rheumatoid arthritis, sepsis, other inflammatory disorders, and many aspects of cancer therapy (18, 19, 92).	TAPI-1 TMI-1, TMI-2, TMI-005 BMS-561392, BMS-566394
ROCK kinase inhibitors	• ROCK kinase regulates the shape and movement of cells by influencing the cytoskeleton (101). • Fasudil inhibits the expression of TLR4, MyD88, and NF-κB, which are key mediators of inflammation. The research showed that kinase ROCK inhibitors could suppress the activation of microglia and could shift astrocytes from an A1 to an A2 phenotype (10, 102, 103). • To increase the activity of Fasudil, researchers are working on its liposomal form (93).	Fasudil
IRAK4 inhibitors	• IRAK4 is an important mediator of inflammatory response, involved in the activation of the TLR and interleukin-1 receptor signal transduction pathways by binding to myeloid differentiation factor 88 (MyD88). • PF-06650833 reduced the levels of inflammatory markers in rodent models of systemic lupus erythematosus and rheumatoid arthritis in phase I clinical studies (94).	PF-06650833